Trial Outcomes & Findings for A Study to Determine the Number of Patients Who Reach Optimal Cholesterol Levels on Each of Three Different Treatments (0653A-121) (NCT NCT00462748)

NCT ID: NCT00462748

Last Updated: 2024-05-16

Results Overview

Fasting LDL-C was the primary efficacy variable. The primary efficacy analysis was based on the proportion of patients achieving a target of \<2mmol/l in fasting LDL-C at study end.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 786 participants
• Primary outcome timeframe: 6 Weeks
• Results posted on: 2024-05-16

Participant Flow

Patients with diabetes, cardiovascular disease (CVD) or a "high risk" of developing CVD and a fasting LDL-C level of ≥2mmol/l, having been on simvastatin 40mg for 6 weeks were assigned to 10/40 mg ezetimibe/simvastatin; 40 mg atorvastatin; 10 mg rosuvastatin (5 mg in elderly/Asian patients (in line with UK SPC)) between 27/03/2007 and 31/03/2008

All patients were subjected to a 6 week run-in period on open label 40 mg simvastatin to stabilise their LDL-C levels. Patients whose LDL-C at the end of this period was below 2.0 mmol/l or who were <75% compliant with run-in medication, were excluded from the study

Participant milestones

Measure	Ezetimibe/Simvastatin ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally
Overall Study STARTED	261	263	262
Overall Study COMPLETED	249	252	251
Overall Study NOT COMPLETED	12	11	11

Reasons for withdrawal

Measure	Ezetimibe/Simvastatin ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally
Overall Study Adverse Event	7	5	9
Overall Study Protocol Violation	0	2	1
Overall Study Withdrew consent	3	3	0
Overall Study Lost to Follow-up	1	1	1
Overall Study Discontinued after 41 days Rx	1	0	0

Baseline Characteristics

A Study to Determine the Number of Patients Who Reach Optimal Cholesterol Levels on Each of Three Different Treatments (0653A-121)

Baseline characteristics by cohort

Measure	Ezetimibe/Simvastatin n=261 Participants ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin n=263 Participants atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin n=262 Participants rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally	Total n=786 Participants Total of all reporting groups
Age, Continuous	64.7 years STANDARD_DEVIATION 8.65 • n=5 Participants	64.2 years STANDARD_DEVIATION 8.44 • n=7 Participants	63.9 years STANDARD_DEVIATION 8.61 • n=5 Participants	64.3 years STANDARD_DEVIATION 8.56 • n=4 Participants
Age, Customized < 70 years	185 participants n=5 Participants	187 participants n=7 Participants	195 participants n=5 Participants	567 participants n=4 Participants
Age, Customized >=70 years	76 participants n=5 Participants	76 participants n=7 Participants	67 participants n=5 Participants	219 participants n=4 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	78 Participants n=7 Participants	84 Participants n=5 Participants	263 Participants n=4 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	185 Participants n=7 Participants	178 Participants n=5 Participants	523 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White	254 Participants n=5 Participants	261 Participants n=7 Participants	257 Participants n=5 Participants	772 Participants n=4 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 Weeks

Population: The Full Analysis Set (FAS) all patients who were: * Randomised * Took at least one dose of double-blind medication * Had a baseline measurement of efficacy * Had a post-baseline measurement of efficacy Patients were analysed according to the treatment group they were randomised, regardless of the treatment they received

Fasting LDL-C was the primary efficacy variable. The primary efficacy analysis was based on the proportion of patients achieving a target of <2mmol/l in fasting LDL-C at study end.

Outcome measures

Measure	Ezetimibe/Simvastatin n=255 Participants ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin n=259 Participants atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin n=258 Participants rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally
Percentage of Patients Achieving a Target of Fasting LDL-C of <2mmol/l at Study End	67.4 Percent	36.3 Percent	17.4 Percent

Adverse Events

Ezetimibe/Simvastatin

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Atorvostatin

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Rosuvastatin

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ezetimibe/Simvastatin ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally
Investigations Platelet count decreased	0.39% 1/259 • Number of events 1	0.00% 0/260	0.00% 0/261
Cardiac disorders Aortic regurgitation	0.39% 1/259 • Number of events 1	0.00% 0/260	0.00% 0/261
General disorders Chest pain	0.39% 1/259 • Number of events 1	0.00% 0/260	0.00% 0/261
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal cancer	0.39% 1/259 • Number of events 1	0.00% 0/260	0.00% 0/261
Skin and subcutaneous tissue disorders Erthematous rash	0.00% 0/259	0.38% 1/260 • Number of events 1	0.00% 0/261
Vascular disorders Areterial haemorrhage	0.00% 0/259	0.38% 1/260 • Number of events 1	0.00% 0/261
Gastrointestinal disorders Rectal bleeding	0.00% 0/259	0.00% 0/260	0.38% 1/261 • Number of events 1
Renal and urinary disorders Hydronephrosis	0.00% 0/259	0.00% 0/260	0.38% 1/261 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/259	0.00% 0/260	0.38% 1/261 • Number of events 1
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/259	0.00% 0/260	0.38% 1/261 • Number of events 1

Other adverse events

Measure	Ezetimibe/Simvastatin ezetimibe (+) simvastatin 10/40mg. once daily tablet formulation, all tablet form, taken orally	Atorvostatin atorvastatin 40mg. once daily tablet formulation, all tablet form, taken orally	Rosuvastatin rosuvastatin 10 mg. once daily tablet formulation, all tablet form, taken orally
Gastrointestinal disorders Diarrhea	2.3% 6/259 • Number of events 6	0.38% 1/260 • Number of events 1	3.1% 8/261 • Number of events 8

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER