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Study Results
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To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 40 mg
This study has been completed.
Study NCT00276484   Information provided by Merck
First Received: January 11, 2006   Last Updated: October 23, 2009   History of Changes
Study Type: Interventional
Study Design: Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment
Condition: Hypercholesterolemia
Interventions: Drug: atorvastatin
Drug: ezetimibe

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Phase III First Patient In: 4/6/2006; Last Patient Last Visit 2/26/2008 96 centers worldwide (US, Canada) Eligible patients include those on a stable dose of atorvastatin 40 mg; or patients with adjusted LDLC pre-screen ranges who were treated with other lipid modifying therapy, or were statin and/or ezetimibe naïve.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Patients received and were blinded to atorvastatin 40 mg for a 4/5- week run-in period.

Patients needed an LDL-C ≥ 70 mg/dL and ≤ 160 mg/dL at Visit 2 (week -1). Eligible patients were randomized at Visit 3 (Week 0) to either atorvastatin 80 mg or addition of ezetimibe 10 mg to their 40 mg dose of atorvastatin for a 6-week treatment period.

Reporting Groups
  Description
Atorvastatin + Ezetemibe Atorvastatin 40 mg + Ezetemibe 10 mg every day for 6 weeks
Atorvastatin Atorvastatin 80 mg every day for 6 weeks

Participant Flow:   Overall Study
  Atorvastatin + Ezetemibe Atorvastatin
STARTED   288     291  
COMPLETED   279     278  
NOT COMPLETED   9     13  
      Adverse Event               4                 7  
      Lost to Follow-up               1                 1  
      Protocol Violation               0                 1  
      Withdrawal by Subject               4                 3  
      Could not take time off work               0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Atorvastatin + Ezetemibe Atorvastatin 40 mg + Ezetemibe 10 mg every day for 6 weeks
Atorvastatin Atorvastatin 80 mg every day for 6 weeks

Baseline Measures
  Atorvastatin + Ezetemibe Atorvastatin Total
Number of Participants  
[units: participants]
 		288 291 579
Age  
[units: years]
Mean ( Full Range ) 		60.6
( 31 to 80 )		 62
( 34 to 79 )		 61.3
( 31 to 80 )
Gender  
[units: participants]
 		     
Female 115 113 228
Male 173 178 351
Race/Ethnicity, Customized  
[units: Participants]
 		     
White 237 232 469
Asian 4 8 12
Black 32 29 61
Multi-Racial 15 22 37
Apolipoprotein A-I  
[units: mg/dL]
Mean ± Standard Deviation 		154.0 ± 25.5 154.6 ± 25.0 154.3 ± 25.3
Apolipoprotein B  
[units: mg/dL]
Mean ± Standard Deviation 		101.3 ± 19.0 102.0 ± 18.8 101.7 ± 18.9
Apolipoprotein B:Apolipoprotein A-I ratio  
[units: Ratio]
Mean ± Standard Deviation 		0.7 ± 0.2 0.7 ± 0.2 0.7 ± 0.2
C Reactive Protein  
[units: mg/dL]
Mean ± Standard Deviation 		1.8 ± 2.7 1.5 ± 3.0 1.6 ± 2.8
High-Density Lipoprotein  
[units: mg/dL]
Mean ± Standard Deviation 		47.4 ± 10.5 47.2 ± 10.6 47.3 ± 10.5
Low-Density Lipoprotein  
[units: mg/dL]
Mean ± Standard Deviation 		88.8 ± 16.2 89.8 ± 16.2 89.4 ± 16.2
Low-Density Lipoprotein-C:High-Density Lipoprotein-C ratio  
[units: Ratio]
Mean ± Standard Deviation 		2.0 ± 0.6 2.0 ± 0.6 2.0 ± 0.6
Non-High-Density Lipoprotein Cholesterol  
[units: mg/dL]
Mean ± Standard Deviation 		117.7 ± 20.8 118.1 ± 21.9 117.9 ± 21.4
Non-High-Density Lipoprotein-C:High-Density Lipoprotein-C ratio  
[units: Ratio]
Mean ± Standard Deviation 		2.6 ± 0.8 2.6 ± 0.8 2.6 ± 0.8
Total Cholesterol  
[units: mg/dL]
Mean ± Standard Deviation 		165.2 ± 21.4 165.3 ± 22.8 165.2 ± 22.1
Total cholesterol:High-Density Lipoprotein-C ratio  
[units: Ratio]
Mean ± Standard Deviation 		3.6 ± 0.8 3.6 ± 0.8 3.6 ± 0.8
Triglycerides  
[units: mg/dL]
Median ± Standard Deviation 		132.5 ± 72.1 134.0 ± 72.1 133.5 ± 72.1



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline to Week 6 in Low-Density Lipoprotein (LDL)-C   [ Baseline and 6 weeks ]
  Show Outcome Measure 1

2.  Secondary:   Percent Change From Baseline to Week 6 in High-Density Lipoprotein Cholesterol (HDL-C)   [ Baseline and 6 weeks ]
  Show Outcome Measure 2

3.  Secondary:   Percent Change From Baseline to Week 6 in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)   [ Baseline and 6 Weeks ]
  Show Outcome Measure 3

4.  Secondary:   Percent Change From Baseline to Week 6 in Total-Cholesterol   [ Baseline and 6 Weeks ]
  Show Outcome Measure 4

5.  Secondary:   Percent Change From Baseline to Week 6 in Triglycerides (TG)   [ Baseline and 6 Weeks ]
  Show Outcome Measure 5

6.  Secondary:   Percent Change From Baseline to Week 6 in Apolipoprotein B (Apo B)   [ Baseline and 6 Weeks ]
  Show Outcome Measure 6

7.  Secondary:   Percent Change From Baseline to Week 6 in Apolipoprotein A-I (Apo A-I)   [ Baseline and 6 Weeks ]
  Show Outcome Measure 7

8.  Secondary:   Percent Change From Baseline to Week 6 in Total-Cholesterol (TC):High-Density Lipoprotein Cholesterol (HDL-C) Ratio   [ Baseline and 6 Weeks ]
  Show Outcome Measure 8

9.  Secondary:   Percent Change From Baseline to Week 6 in Low-Density Lipoprotein-Cholesterol:High-Density Lipoprotein-Cholesterol (LDL-C:HDL-C) Ratio   [ Baseline and 6 Weeks ]
  Show Outcome Measure 9

10.  Secondary:   Percent Change From Baseline to Week 6 in Apolipoprotein B:Apolipoprotein A-I (Apo B:Apo A-I) Ratio   [ Baseline and 6 Weeks ]
  Show Outcome Measure 10

11.  Secondary:   Percent Change From Baseline to Week 6 in Non-High-Density Lipoprotein-Cholesterol:High-Density Lipoprotein-Cholesterol (Non-HDL-C:HDL-C) Ratio   [ Baseline and 6 Weeks ]
  Show Outcome Measure 11

12.  Secondary:   Percent Change From Baseline to Week 6 in C Reactive Protein (CRP)   [ Baseline and 6 Weeks ]
  Show Outcome Measure 12

13.  Secondary:   Number of Patients Who Attained Target Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL at Week 6   [ 6 Weeks ]
  Show Outcome Measure 13


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Atorvastatin + Ezetemibe Atorvastatin 40 mg + Ezetemibe 10 mg every day for 6 weeks
Atorvastatin Atorvastatin 80 mg every day for 6 weeks

Other Adverse Events
  Atorvastatin + Ezetemibe Atorvastatin
Total, other (not including serious) adverse events    
# participants affected 63   61  
Blood and lymphatic system disorders    
Anaemia   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Cardiac disorders    
Cardiac failure congestive   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Coronary artery disease   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Myocardial infarction   * A
      # participants affected / at risk
3/286 (1.05%)  
1/289 (0.35%)  
Ear and labyrinth disorders    
Vertigo   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Eye disorders    
Retinal detachment   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Vision blurred   * A
      # participants affected / at risk
2/286 (0.70%)  
1/289 (0.35%)  
Visual disturbance   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Gastrointestinal disorders    
Abdominal discomfort   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Abdominal distension   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Abdominal pain   * A
      # participants affected / at risk
2/286 (0.70%)  
2/289 (0.69%)  
Abdominal pain upper   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Constipation   * A
      # participants affected / at risk
1/286 (0.35%)  
2/289 (0.69%)  
Dental caries   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Diarrhoea   * A
      # participants affected / at risk
0/286 (0.00%)  
6/289 (2.08%)  
Diverticulum   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Dyspepsia   * A
      # participants affected / at risk
0/286 (0.00%)  
2/289 (0.69%)  
Dysphagia   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Flatulence   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Gastritis   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Gastrooesophageal reflux disease   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Gingivitis   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Nausea   * A
      # participants affected / at risk
2/286 (0.70%)  
2/289 (0.69%)  
Stomach discomfort   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Vomiting   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
General disorders    
Chest pain   * A
      # participants affected / at risk
3/286 (1.05%)  
2/289 (0.69%)  
Fatigue   * A
      # participants affected / at risk
0/286 (0.00%)  
4/289 (1.38%)  
Hernia obstructive   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Non-cardiac chest pain   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Oedema peripheral   * A
      # participants affected / at risk
2/286 (0.70%)  
1/289 (0.35%)  
Pyrexia   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Alanine aminotransferase   * A
      # participants affected / at risk
2/286 (0.70%)  
2/289 (0.69%)  
Aspartate aminotransferase   * A
      # participants affected / at risk
2/286 (0.70%)  
2/289 (0.69%)  
Blood bilirubin increased   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Blood creatine phosphokinase increased   * A
      # participants affected / at risk
2/286 (0.70%)  
0/289 (0.00%)  
Blood potassium increased   * A
      # participants affected / at risk
2/286 (0.70%)  
0/289 (0.00%)  
Blood uric acid increased   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Carotid pulse decreased   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Gamma-glutamyltransferase increased   * A
      # participants affected / at risk
2/286 (0.70%)  
1/289 (0.35%)  
Cataract operation   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Inguinal hernia repair   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Hepatobiliary disorders    
Cholelithiasis   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Immune system disorders    
Seasonal allergy   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Infections and infestations    
Bronchitis   * A
      # participants affected / at risk
4/286 (1.40%)  
1/289 (0.35%)  
Chronic sinusitis   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Conjunctivitis infective   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Gastroenteritis viral   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Nasopharyngitis   * A
      # participants affected / at risk
4/286 (1.40%)  
1/289 (0.35%)  
Pharyngitis   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Pharyngitis streptococcal   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Pneumonia   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Sinusitis   * A
      # participants affected / at risk
2/286 (0.70%)  
1/289 (0.35%)  
Upper respiratory tract infection   * A
      # participants affected / at risk
1/286 (0.35%)  
7/289 (2.42%)  
Urinary tract infection   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Injury, poisoning and procedural complications    
Back injury   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Burns second degree   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Contusion   * A
      # participants affected / at risk
2/286 (0.70%)  
0/289 (0.00%)  
Joint sprain   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Overdose   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Scratch   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Thermal burn   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Tooth fracture   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Musculoskeletal and connective tissue disorders    
Arthralgia   * A
      # participants affected / at risk
0/286 (0.00%)  
4/289 (1.38%)  
Back pain   * A
      # participants affected / at risk
0/286 (0.00%)  
3/289 (1.04%)  
Intervertebral disc degeneration   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Joint effusion   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Muscle spasms   * A
      # participants affected / at risk
0/286 (0.00%)  
2/289 (0.69%)  
Musculoskeletal chest pain   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Musculoskeletal pain   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Myalgia   * A
      # participants affected / at risk
1/286 (0.35%)  
5/289 (1.73%)  
Pain in extremity   * A
      # participants affected / at risk
4/286 (1.40%)  
3/289 (1.04%)  
Nervous system disorders    
Carotid artery stenosis   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Cerebellar ataxia   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Dizziness   * A
      # participants affected / at risk
3/286 (1.05%)  
2/289 (0.69%)  
Headache   * A
      # participants affected / at risk
4/286 (1.40%)  
2/289 (0.69%)  
Migraine   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Paraesthesia   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Presyncope   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Sciatica   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Syncope   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Psychiatric disorders    
Anxiety   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Confusional state   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Insomnia   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Mental status changes   † A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Renal and urinary disorders    
Calculus bladder   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Nephrolithiasis   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Renal cyst   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Renal failure   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Reproductive system and breast disorders    
Benign prostatic hyperplasia   † A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Erectile dysfunction   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Respiratory, thoracic and mediastinal disorders    
Asthma   † A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Bronchospasm   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Chronic obstructive pulmonary disease   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Cough   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Dyspnoea   * A
      # participants affected / at risk
3/286 (1.05%)  
1/289 (0.35%)  
Nasal congestion   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Pharyngolaryngeal pain   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Pulmonary haemorrhage   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Skin and subcutaneous tissue disorders    
Pruritus   * A
      # participants affected / at risk
1/286 (0.35%)  
1/289 (0.35%)  
Rash erythematous   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Vascular disorders    
Haematoma   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
Hypertension   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Hypertensive crisis   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Hypotension   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Labile hypertension   * A
      # participants affected / at risk
1/286 (0.35%)  
0/289 (0.00%)  
Peripheral vascular disorder   * A
      # participants affected / at risk
0/286 (0.00%)  
1/289 (0.35%)  
† Indicates events were collected by systematic assessment.
* Indicates events were collected by non-systematic assessment.
A Term from vocabulary, MedDRA


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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Senior Vice President, Clinical and Quantitative Sciences
Organization: Merck & Co., Inc.
phone: 1-800-672-6372


Publications:
Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, Tomassini JE, Tershakovec AM. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1495-501. Epub 2008 Oct 23.


Responsible Party: Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers: 2005_105, MK0653-090
Study First Received: January 11, 2006
Results First Received: February 6, 2009
Last Updated: October 23, 2009
ClinicalTrials.gov Identifier: NCT00276484     History of Changes
Health Authority: United States: Food and Drug Administration





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