Coadministration of Ezetimibe and Simvastatin in Patients With Primary Hypercholesterolemia (P05457)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00653523
• Collaborator: (none)
• Enrollment: 151
• Arm: 1
• Actual Duration (Months): 18

Study Details

Study Description

Brief Summary

Evaluate the safety of the long-term (1 year) coadministration of ezetimibe and simvastatin in patients 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
Hypercholesterolemia	Drug: Ezetimibe; Drug: Simvastatin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Long-term Study of Coadministration of Ezetimibe and Simvastatin in Patients With Primary Hypercholesterolemia Who Have Not Reached LDL-cholesterol Target With HMG-CoA Reductase Inhibitors
• Actual Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ezetimibe + Simvastatin Ezetimibe 10 mg + Simvastatin 20 mg	Drug: Ezetimibe; Ezetimibe 10 mg once daily; Other Names: SCH 58235 ; Drug: Simvastatin; Simvastatin 20 mg daily

Outcome Measures

Primary Outcome Measures

1. 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 treatment-related was considered an adverse reaction.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with hypercholesterolemia who satisfy the following criteria:

• Patients who have used any of the following HMG-CoA reductase inhibitors (hereinafter referred to as "statins") for 4 weeks or longer before the start of the observation period and whose LDL-cholesterol level during the treatment had not reached lipid management target indicated below

• Age: 20 years of age or older (at the time of obtaining informed consent)

• Sex: both males and females

• Inpatient/outpatient: Out-patients

Exclusion Criteria:

• Patients for whom any of the following is applicable:

• Patients whose fasted triglyceride level measured at the start of the observation period or the treatment period exceeds 500 mg/dL

• Patients with homozygous familial hypercholesterolemia

• Patients with creatine phosphokinase (CPK) > 2x upper limit of normal (ULN) measured at the start of the observation period or the treatment period.

• Patients with serious hepatic disorder, or patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN measured at the start of the observation period or the treatment period.

• Patients with a history of hypersensitivity to any ingredient of ezetimibe tablets or simvastatin tablets

• Pregnant, nursing women, women who may be pregnant, or patients wishing to be pregnant during the study.

• Patients 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 patient 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.)

• Patients who are using cyclosporine from after the start of the observation period

• Patients who are using any of the following drug from after the start of the observation period: itraconazole, miconazole, atazanavir, saquinavir mesilate

• Patients with a history of ezetimibe use

• Patients with hyperlipidemia associated with the following diseases:

• Hypothyroidism

• Obstructive gall bladder or biliary disease

• Chronic renal failure

• Pancreatitis

• Patients with hyperlipidemia associated with concomitant use of drugs having adverse effect on serum lipids, etc

• Patients who have received an investigational drug within 4 weeks of the start of the observation period

• Other patients 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.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00653523
• Other Study ID Numbers: P05457
• First Posted: Apr 7, 2008
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hypercholesterolemia; Simvastatin; Ezetimibe

Study Results

Participant Flow

Arm/Group Title	Ezetimibe + Simvastatin
Arm/Group Description	Ezetimibe 10 mg + Simvastatin 20 mg level below what was specified in inclusion criterion level >2x upper limit of normal at start of treatment level >=3x upper limit of normal after start of treatment did not resolve or improve after dose reduction of simvastatin
Period Title: Overall Study
STARTED	151
COMPLETED	132
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Ezetimibe + Simvastatin
Arm/Group Description	Ezetimibe 10 mg + Simvastatin 20 mg
Overall Participants	151
Age, Customized (Number) [Number]
Number [Participants]	151 100%
Sex: Female, Male (Count of Participants)
Female	82 54.3%
Male	69 45.7%
Region of Enrollment (participants) [Number]
Japan	151 100%

Outcome Measures

1. Primary Outcome

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 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 + Simvastatin
Arm/Group Description	Ezetimibe 10 mg + Simvastatin 20 mg
Measure Participants	151
Adverse Events	143 94.7%
Adverse Reactions	36 23.8%

Adverse Events

Arm/Group Title	Ezetimibe+Simvastatin
Arm/Group Description
All Cause Mortality
	Ezetimibe+Simvastatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ezetimibe+Simvastatin
	Affected / at Risk (%)	# Events
Total	17/151 (11.3%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	1/151 (0.7%)	1
ANGINA UNSTABLE	1/151 (0.7%)	1
HYPERTROPHIC CARDIOMYOPATHY	1/151 (0.7%)	1
Eye disorders
EYE PAIN	1/151 (0.7%)	1
Infections and infestations
PNEUMONIA	1/151 (0.7%)	1
Injury, poisoning and procedural complications
CORONARY ARTERY RESTENOSIS	3/151 (2%)	3
IN-STENT CORONARY ARTERY RESTENOSIS	1/151 (0.7%)	2
Metabolism and nutrition disorders
DIABETES MELLITUS INADEQUATE CONTROL	1/151 (0.7%)	1
Musculoskeletal and connective tissue disorders
ROTATOR CUFF SYNDROME	1/151 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	1/151 (0.7%)	1
UTERINE CANCER	1/151 (0.7%)	1
Nervous system disorders
SUBARACHNOID HAEMORRHAGE	1/151 (0.7%)	1
Skin and subcutaneous tissue disorders
ACTINIC KERATOSIS	1/151 (0.7%)	1
Surgical and medical procedures
ARTERIAL STENT INSERTION	1/151 (0.7%)	2
Vascular disorders
AORTIC DISSECTION	1/151 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Ezetimibe+Simvastatin
	Affected / at Risk (%)	# Events
Total	127/151 (84.1%)
Gastrointestinal disorders
CONSTIPATION	9/151 (6%)	9
Infections and infestations
BRONCHITIS	20/151 (13.2%)	25
NASOPHARYNGITIS	46/151 (30.5%)	73
PHARYNGITIS	10/151 (6.6%)	13
Investigations
ALANINE AMINOTRANSFERASE INCREASED	26/151 (17.2%)	32
ASPARTATE AMINOTRANSFERASE INCREASED	10/151 (6.6%)	11
BLOOD AMYLASE INCREASED	12/151 (7.9%)	14
BLOOD CREATINE PHOSPHOKINASE INCREASED	27/151 (17.9%)	33
C-REACTIVE PROTEIN INCREASED	41/151 (27.2%)	47
GAMMA-GLUTAMYLTRANSFERASE INCREASED	14/151 (9.3%)	14
GLYCOSYLATED HAEMOGLOBIN INCREASED	10/151 (6.6%)	11
MYOGLOBIN BLOOD INCREASED	21/151 (13.9%)	21
WHITE BLOOD CELL COUNT INCREASED	12/151 (7.9%)	12
Metabolism and nutrition disorders
DIABETES MELLITUS	8/151 (5.3%)	8
HYPOGLYCAEMIA	9/151 (6%)	14
Musculoskeletal and connective tissue disorders
ARTHRALGIA	15/151 (9.9%)	15
BACK PAIN	17/151 (11.3%)	17
MUSCLE SPASMS	14/151 (9.3%)	20
MUSCULOSKELETAL STIFFNESS	13/151 (8.6%)	14
PAIN IN EXTREMITY	11/151 (7.3%)	12
Nervous system disorders
HEADACHE	12/151 (7.9%)	14
Respiratory, thoracic and mediastinal disorders
UPPER RESPIRATORY TRACT INFLAMMATION	11/151 (7.3%)	13

Limitations/Caveats

[Not Specified]

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.