Coadministration of Ezetimibe and Atorvastatin in Patients With Primary Hypercholesterolemia (P05456)
Study Details
Study Description
Brief Summary
Evaluate the safety of the long-term (1 year) coadministration of ezetimibe and atorvastatin in participants with hypercholesterolemia who have not reached low density lipoprotein (LDL)-cholesterol target with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ezetimibe + Atorvastatin Ezetimibe 10 mg + Atorvastatin 20 mg |
Drug: Ezetimibe
Ezetimibe 10 mg once daily
Other Names:
Drug: atorvastatin
atorvastatin 20 mg once daily
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events and Adverse Reactions [Throughout 1 year of study]
An adverse event is any unfavorable medical event occurring in a subject to whom an investigational product is administered, and a causal relationship between the administered investigational product and an adverse event is not always clarified. That is, an adverse event is any unfavorable or unintended sign (including an abnormal change in laboratory test values), symptom, or disease, and a causal relationship to the relevant investigational product is not considered. Any adverse event that was considered treatment-related was considered an adverse reaction.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants with hypercholesterolemia who satisfy the following criteria:
-
Participants who have used any of the following 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (hereinafter referred to as "statins") for 4 weeks or longer before the start of the observation period and whose low density lipoprotein (LDL)-cholesterol level during the treatment had not reached lipid management target
-
Age: 20 years of age or older (at the time of obtaining informed consent)
-
Sex: both males and females
-
Inpatient/outpatient: Out-patient
Exclusion Criteria:
-
Participants for whom any of the following is applicable:
-
Participants whose fasted triglyceride level measured at the start of the observation period or the treatment period exceeds 500 mg/dL
-
Participants with homozygous familial hypercholesterolemia
-
Participants with creatine phosphokinase (CPK) > 2x upper limit of normal (ULN) measured at the start of the observation period or the treatment period.
-
Participants with serious hepatic disorder, or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN measured at the start of the observation period or the treatment period.
-
Participants with a history of hypersensitivity to any ingredient of ezetimibe tablets or atorvastatin tablets
-
Pregnant, nursing women, women who may be pregnant, or participants wishing to be pregnant during the study.
-
Participants who have discontinued use of serum lipid lowering agents for less than 4 weeks at the start of the treatment period (8 weeks in the case of probucol). (However, if the participant had taken a serum lipid lowering agent before the test conducted at the start of the observation period, a period of discontinuation of 27 days, or 55 days in the case of probucol, is allowed.)
-
Participants who are using cyclosporine from after the start of the observation period
-
Participants with a history of ezetimibe use
-
Participants with hyperlipidemia associated with the following diseases:
-
Hypothyroidism
-
Obstructive gall bladder or biliary disease
-
Chronic renal failure
-
Pancreatitis
-
Participants with hyperlipidemia associated with concomitant use of drugs having adverse effect on serum lipids, etc
-
Participants who have received an investigational drug within 4 weeks of the start of the observation period
-
Other participants deemed not appropriate for study entry by the investigator
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P05456
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants did not Complete the Study: level below what was specified in inclusion criterion level >500 mg/dL at start of treatment level >2x upper limit of normal at start of treatment level >=3x upper limit of normal after start of treatment Adverse reactions did not improve or resolve after dose reduction of atorvastatin |
| Arm/Group Title | Ezetimibe + Atorvastatin |
|---|---|
| Arm/Group Description | Ezetimibe 10 mg once daily + Atorvastatin 20 mg once daily |
| Period Title: Overall Study | |
| STARTED | 146 |
| COMPLETED | 114 |
| NOT COMPLETED | 32 |
Baseline Characteristics
| Arm/Group Title | Ezetimibe + Atorvastatin |
|---|---|
| Arm/Group Description | Ezetimibe 10 mg once daily + Atorvastatin 20 mg once daily |
| Overall Participants | 146 |
| Age, Customized (Number) [Number] | |
| Number [Participants] |
146
100%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
79
54.1%
|
| Male |
67
45.9%
|
| Region of Enrollment (participants) [Number] | |
| Japan |
146
100%
|
Outcome Measures
| Title | Number of Participants With Adverse Events and Adverse Reactions |
|---|---|
| Description | An adverse event is any unfavorable medical event occurring in a subject to whom an investigational product is administered, and a causal relationship between the administered investigational product and an adverse event is not always clarified. That is, an adverse event is any unfavorable or unintended sign (including an abnormal change in laboratory test values), symptom, or disease, and a causal relationship to the relevant investigational product is not considered. Any adverse event that was considered treatment-related was considered an adverse reaction. |
| Time Frame | Throughout 1 year of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ezetimibe + Atorvastatin |
|---|---|
| Arm/Group Description | Ezetimibe 10 mg once daily + Atorvastatin 20 mg once daily |
| Measure Participants | 146 |
| Adverse Events |
141
96.6%
|
| Adverse Reactions |
61
41.8%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Ezetimibe+Atorvastatin | |
| Arm/Group Description | ||
All Cause Mortality |
||
| Ezetimibe+Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Ezetimibe+Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 11/146 (7.5%) | |
| Cardiac disorders | ||
| SICK SINUS SYNDROME | 1/146 (0.7%) | 1 |
| Eye disorders | ||
| GLAUCOMA | 1/146 (0.7%) | 1 |
| RETINAL ARTERY OCCLUSION | 1/146 (0.7%) | 1 |
| Infections and infestations | ||
| GASTROENTERITIS | 1/146 (0.7%) | 1 |
| Injury, poisoning and procedural complications | ||
| HUMERUS FRACTURE | 1/146 (0.7%) | 1 |
| IN-STENT CORONARY ARTERY RESTENOSIS | 1/146 (0.7%) | 1 |
| RIB FRACTURE | 1/146 (0.7%) | 1 |
| ULNA FRACTURE | 1/146 (0.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| BREAST CANCER | 1/146 (0.7%) | 1 |
| LYMPHOMA | 1/146 (0.7%) | 1 |
| PANCREATIC NEOPLASM | 1/146 (0.7%) | 1 |
| PROSTATE CANCER | 1/146 (0.7%) | 1 |
| Nervous system disorders | ||
| CEREBRAL HAEMORRHAGE | 1/146 (0.7%) | 1 |
| Reproductive system and breast disorders | ||
| BENIGN PROSTATIC HYPERPLASIA | 1/146 (0.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| ERYTHEMA MULTIFORME | 1/146 (0.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Ezetimibe+Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 132/146 (90.4%) | |
| Gastrointestinal disorders | ||
| CONSTIPATION | 10/146 (6.8%) | 10 |
| GASTRITIS | 10/146 (6.8%) | 11 |
| General disorders | ||
| MALAISE | 10/146 (6.8%) | 16 |
| Immune system disorders | ||
| SEASONAL ALLERGY | 8/146 (5.5%) | 9 |
| Infections and infestations | ||
| BRONCHITIS | 11/146 (7.5%) | 11 |
| GASTROENTERITIS | 9/146 (6.2%) | 11 |
| NASOPHARYNGITIS | 53/146 (36.3%) | 97 |
| PHARYNGITIS | 8/146 (5.5%) | 12 |
| Investigations | ||
| ALANINE AMINOTRANSFERASE INCREASED | 48/146 (32.9%) | 59 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 16/146 (11%) | 18 |
| BILIRUBIN CONJUGATED INCREASED | 18/146 (12.3%) | 26 |
| BLOOD BILIRUBIN INCREASED | 11/146 (7.5%) | 16 |
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 20/146 (13.7%) | 24 |
| C-REACTIVE PROTEIN INCREASED | 31/146 (21.2%) | 39 |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 24/146 (16.4%) | 26 |
| GLYCOSYLATED HAEMOGLOBIN INCREASED | 9/146 (6.2%) | 9 |
| MYOGLOBIN BLOOD INCREASED | 17/146 (11.6%) | 23 |
| MYOGLOBIN URINE PRESENT | 17/146 (11.6%) | 18 |
| WEIGHT INCREASED | 9/146 (6.2%) | 9 |
| WHITE BLOOD CELL COUNT INCREASED | 11/146 (7.5%) | 13 |
| Musculoskeletal and connective tissue disorders | ||
| ARTHRALGIA | 11/146 (7.5%) | 11 |
| BACK PAIN | 12/146 (8.2%) | 15 |
| MUSCULOSKELETAL STIFFNESS | 8/146 (5.5%) | 8 |
| Nervous system disorders | ||
| HEADACHE | 8/146 (5.5%) | 9 |
| Respiratory, thoracic and mediastinal disorders | ||
| RHINITIS ALLERGIC | 10/146 (6.8%) | 12 |
| UPPER RESPIRATORY TRACT INFLAMMATION | 18/146 (12.3%) | 23 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Principal Investigator (PI) agrees, for a period of 5 years following the Effective Date, to retain the Disclosure made to it by or on behalf of Sponsor (SPKK), in confidence and not to disclose it to any third party. PI further agrees that during such time period it will not, either directly or indirectly, use the Disclosure for any purpose(s) other than that indicated herein without the prior written consent of SPKK.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | |
| ClinicalTrialsDisclosure@merck.com |
- P05456