Trial Outcomes & Findings for Safety and Efficacy Study Comparing ABT-143 to Simvastatin in Subjects With Elevated Levels of Low Density Lipoprotein Cholesterol ("Bad Cholesterol") and Triglycerides (NCT NCT00812955)

NCT ID: NCT00812955

Last Updated: 2012-10-03

Results Overview

The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following two treatment groups: ABT-143 capsules 20/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 474 participants
• Primary outcome timeframe: Baseline to 8 weeks
• Results posted on: 2012-10-03

Participant Flow

474 subjects were randomized and treated at 111 sites in the United States between 29 December 2008 and 14 May 2009.

Participant milestones

Measure	Simvastatin Capsules 40 mg Simvastatin capsules 40 mg once daily for 8 weeks	ABT-143 Capsules 5/135 mg ABT-143 capsules 5/135 mg once daily for 8 weeks	ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks
Overall Study STARTED	119	118	119	118
Overall Study COMPLETED	109	111	113	110
Overall Study NOT COMPLETED	10	7	6	8

Reasons for withdrawal

Measure	Simvastatin Capsules 40 mg Simvastatin capsules 40 mg once daily for 8 weeks	ABT-143 Capsules 5/135 mg ABT-143 capsules 5/135 mg once daily for 8 weeks	ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks
Overall Study Adverse Event	7	6	3	4
Overall Study Lost to Follow-up	2	1	1	2
Overall Study Withdrawal by Subject	1	0	1	2
Overall Study randomized in error	0	0	1	0

Baseline Characteristics

Safety and Efficacy Study Comparing ABT-143 to Simvastatin in Subjects With Elevated Levels of Low Density Lipoprotein Cholesterol ("Bad Cholesterol") and Triglycerides

Baseline characteristics by cohort

Measure	Simvastatin Capsules 40 mg n=119 Participants Simvastatin capsules 40 mg once daily for 8 weeks	ABT-143 Capsules 5/135 mg n=118 Participants ABT-143 capsules 5/135 mg once daily for 8 weeks	ABT-143 Capsules 10/135 mg n=119 Participants ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg n=118 Participants ABT-143 capsules 20/135 mg once daily for 8 weeks	Total n=474 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	92 Participants n=5 Participants	91 Participants n=7 Participants	95 Participants n=5 Participants	95 Participants n=4 Participants	373 Participants n=21 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	27 Participants n=7 Participants	24 Participants n=5 Participants	23 Participants n=4 Participants	101 Participants n=21 Participants
Age Continuous	56.8 years STANDARD_DEVIATION 9.77 • n=5 Participants	56.8 years STANDARD_DEVIATION 8.91 • n=7 Participants	56.6 years STANDARD_DEVIATION 9.27 • n=5 Participants	56.0 years STANDARD_DEVIATION 10.41 • n=4 Participants	56.6 years STANDARD_DEVIATION 9.58 • n=21 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	62 Participants n=7 Participants	59 Participants n=5 Participants	60 Participants n=4 Participants	252 Participants n=21 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	56 Participants n=7 Participants	60 Participants n=5 Participants	58 Participants n=4 Participants	222 Participants n=21 Participants
Region of Enrollment United States	119 participants n=5 Participants	118 participants n=7 Participants	119 participants n=5 Participants	118 participants n=4 Participants	474 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to 8 weeks

Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.

The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following two treatment groups:

ABT-143 capsules 20/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.

Outcome measures

Measure	Simvastatin Capsules 40 mg n=114 Participants Simvastatin capsules 40 mg	ABT-143 Capsules 20/135 mg n=113 Participants ABT-143 capsules 20/135 mg	ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set)	-32.8 percent change Standard Error 1.59	-47.2 percent change Standard Error 1.60	—	—

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.

The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 10/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.

Outcome measures

Measure	Simvastatin Capsules 40 mg n=114 Participants Simvastatin capsules 40 mg	ABT-143 Capsules 20/135 mg n=115 Participants ABT-143 capsules 20/135 mg	ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 10/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set)	-32.8 percent change Standard Error 1.59	-46.0 percent change Standard Error 1.59	—	—

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.

The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 5/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.

Outcome measures

Measure	Simvastatin Capsules 40 mg n=114 Participants Simvastatin capsules 40 mg	ABT-143 Capsules 20/135 mg n=114 Participants ABT-143 capsules 20/135 mg	ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 5/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set)	-32.8 percent change Standard Error 1.59	-38.9 percent change Standard Error 1.59	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 8 weeks

Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for triglycerides. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.

The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for median percent change in triglycerides from Baseline to the Final Visit for the full analysis set.

Outcome measures

Measure	Simvastatin Capsules 40 mg n=114 Participants Simvastatin capsules 40 mg	ABT-143 Capsules 20/135 mg n=114 Participants ABT-143 capsules 20/135 mg	ABT-143 Capsules 10/135 mg n=115 Participants ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg n=113 Participants ABT-143 capsules 20/135 mg once daily for 8 weeks
Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set)	-20.8 percent change Interval -41.3 to 1.9	-42.7 percent change Interval -54.5 to -30.4	-44.6 percent change Interval -55.4 to -31.6	-50.0 percent change Interval -57.5 to -32.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 8 weeks

Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for HDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.

The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for mean percent change in high-density lipoprotein cholesterol from Baseline to the Final Visit for the full analysis set.

Outcome measures

Measure	Simvastatin Capsules 40 mg n=114 Participants Simvastatin capsules 40 mg	ABT-143 Capsules 20/135 mg n=114 Participants ABT-143 capsules 20/135 mg	ABT-143 Capsules 10/135 mg n=115 Participants ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg n=113 Participants ABT-143 capsules 20/135 mg once daily for 8 weeks
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set)	9.6 percent change Standard Error 1.56	16.2 percent change Standard Error 1.56	14.0 percent change Standard Error 1.55	15.7 percent change Standard Error 1.56

Adverse Events

Simvastatin Capsules 40 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

ABT-143 Capsules 5/135 mg

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

ABT-143 Capsules 10/135 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

ABT-143 Capsules 20/135 mg

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Simvastatin Capsules 40 mg n=119 participants at risk Simvastatin capsules 40 mg once daily for 8 weeks	ABT-143 Capsules 5/135 mg n=118 participants at risk ABT-143 capsules 5/135 mg once daily for 8 weeks	ABT-143 Capsules 10/135 mg n=119 participants at risk ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg n=118 participants at risk ABT-143 capsules 20/135 mg once daily for 8 weeks
Cardiac disorders Angina Pectoris	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Cardiac disorders Myocardial Infarction	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Cardiac disorders Tachycardia	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Gastrointestinal disorders Abdominal Hernia	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.84% 1/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
General disorders Chest Pain	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Nervous system disorders Syncope	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.85% 1/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.00% 0/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.

Other adverse events

Measure	Simvastatin Capsules 40 mg n=119 participants at risk Simvastatin capsules 40 mg once daily for 8 weeks	ABT-143 Capsules 5/135 mg n=118 participants at risk ABT-143 capsules 5/135 mg once daily for 8 weeks	ABT-143 Capsules 10/135 mg n=119 participants at risk ABT-143 capsules 10/135 mg once daily for 8 weeks	ABT-143 Capsules 20/135 mg n=118 participants at risk ABT-143 capsules 20/135 mg once daily for 8 weeks
Gastrointestinal disorders Nausea	1.7% 2/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	5.9% 7/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	2.5% 3/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	5.1% 6/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Infections and infestations Upper Respiratory Tract Infection	0.84% 1/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	1.7% 2/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	1.7% 2/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	5.9% 7/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.
Nervous system disorders Headache	6.7% 8/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	4.2% 5/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	0.84% 1/119 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.	5.9% 7/118 • 18 weeks Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Serious adverse events were collected from the time the participant signed the informed consent until 30 calendar days following discontinuation of study drug.

Additional Information

Gerard Lynch

AstraZeneca

Phone: +44 1509 645 895

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.
• Publication restrictions are in place

Restriction type: OTHER