Adding Ezetimibe Tablet to Ongoing Treatment With Atorvastatin in Subjects With High Cholesterol and Multiple Coronary Heart Disease Risk Factors (Study P04060)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00319449
• Collaborator: PT. Schering-Plough. Tbk Indonesia (Other)
• Enrollment: 22
• Arms: 2
• Duration (Months): 13

Study Details

Study Description

Brief Summary

This study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe 10 mg coadministered with atorvastatin 10 mg versus atorvastatin 10 mg in Indonesian population with primary hypercholesterolemia.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia; Coronary Arteriosclerosis	Drug: Ezetimibe; Drug: Placebo; Drug: Atorvastatin 10 mg	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Single Center, Randomized, Parallel Groups, Placebo-Controlled Study Comparing The Efficacy, Safety, And Tolerability Of The Daily Co-administration Of Ezetimibe 10 Mg Or Ezetimibe Placebo To Ongoing Treatment With Atorvastatin 10 Mg In Subjects With Primary Hypercholesterolemia And Multiple Coronary Heart Disease Risk Factors in Indonesian Population.
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Oct 1, 2006
• Actual Study Completion Date: Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ezetimibe 10 mg Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Drug: Ezetimibe; 10 mg ezetimibe, orally, daily for 6 weeks, added to ongoing treatment with 10 mg atorvastatin; Drug: Atorvastatin 10 mg; 10 mg/day atorvastatin, orally, (ongoing treatment in participants)
Placebo Comparator: Placebo 10 mg Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Drug: Placebo; 10 mg/day matching placebo to ezetimibe, orally, daily for 6 weeks, added to ongoing 10 mg atorvastatin; Drug: Atorvastatin 10 mg; 10 mg/day atorvastatin, orally, (ongoing treatment in participants)

Outcome Measures

Primary Outcome Measures

1. Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg [Baseline and 6 weeks]

   12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - [HDL-C + TG/5]) before and after treatment.

Secondary Outcome Measures

1. Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL) [6 weeks post treatment]

   12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - [HDL-C + TG/5] after treatment for 6 weeks.

2. High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg [6 weeks post treatment]

   12-hour fasting blood samples were collected in participants and the high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol was measured with the basic lipid panel test.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have an LDL-C concentration >= 3.3 mmol/L (130 mg/dL) to <= 4.9 mmol/L (190 mg/dL) using the Freidewald calculation.

• Participants must have triglyceride concentrations of < 3.99 mmol/L (350 mg/dL).

• Participants must have two or more coronary heart disease risk factors listed below:

• Current cigarette smoking

• Hypertension (BP >= 140/90 mmHg or on antihypertensive medication)

• Low HDL cholesterol (< 40 mg/dL)

• Family history of premature CHD (CHD in male first degree relative < 55 years; CHD in female first degree relative < 65 years)

• Age (Men >= 45 years; women >= 55 years)

• Participant must be currently taking atorvastatin 10 mg daily and by history has taken 80% of daily doses for the 6 weeks prior to participating.

• Participants must have liver transaminases (ALT, AST) < 50% above the upper limit of normal, with no active liver disease, and CK < 50% above the upper limit of normal.

• Participants must have maintained a cholesterol lowering diet, exercise program, and stable weight for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study.

• Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study.

Exclusion Criteria:

• Participants who meet any of the following criteria will be excluded:

• Body mass index (BMI = weight [kg]/height2[m]) is >= 30 Kg/m2.

• Consume > 14 alcoholic drinks per week.

• Women who are pregnant or nursing.

• Congestive heart failure defined by NYHA as Class III or IV.

• Uncontrolled cardiac arrhythmia.

• Coronary heart disease (CHD).

• Unstable or severe peripheral artery disease within 3 months of participating

• Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm Hg or diastolic > 100 mm Hg.

• Type I or Type II diabetes mellitus.

• Secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism.

• Impaired renal function (creatinine > 2.0 mg/dL) or nephrotic syndrome.

• Known HIV positive.

• Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas).

• History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.

• Participants who are on any of the following concomitant medications:

• Participants who are on medications that are potent inhibitors of CYP3A4, including cyclosporine, systemic itraconazole, fluconazole, and ketoconazole, erythromycin or clarithromycin, nefazodone, mibefradil, protease inhibitors and large amounts of grapefruit juice (> 1 quart/day).

• Participants who are on lipid-lowering agents (other atorvastatin): niacin (> 200 mg/day)

• Participants who are on over the counter lipid lowering agents such as fish oils, garlic and cholestin

• Participants who are on oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease and the subject is on a stable regimen for at least 6 weeks.

• Participants who are currently using psyllium, other fiber-based laxatives, and/or any other OTC therapy known to affect serum lipid levels (phytosterol margarine), and have not been on a stable regimen for at least 5 weeks and who do not agree to remain on this regimen throughout the study.

• Participant who are currently using orlistat or sibutramine.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co
• PT. Schering-Plough. Tbk Indonesia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00319449
• Other Study ID Numbers: P04060
• First Posted: Apr 27, 2006
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis; Hypercholesterolemia; Atorvastatin; Ezetimibe

Study Results

Participant Flow

Arm/Group Title	Ezetimibe 10 mg	Placebo 10 mg
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.
Period Title: Overall Study
STARTED	10	12
COMPLETED	8	12
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Ezetimibe 10 mg	Placebo 10 mg	Total
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Total of all reporting groups
Overall Participants	10	12	22
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.4 (12.1)	52.2 (10.4)	54.5 (11.3)
Age, Customized (Number) [Number]
18 to <65 years	7 70%	11 91.7%	18 81.8%
65 or older	3 30%	1 8.3%	4 18.2%
Sex: Female, Male (Count of Participants)
Female	3 30%	5 41.7%	8 36.4%
Male	7 70%	7 58.3%	14 63.6%
Region of Enrollment (participants) [Number]
Indonesia	10 100%	12 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg
Description	12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - [HDL-C + TG/5]) before and after treatment.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Ezetimibe 10 mg	Placebo 10 mg
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.
Measure Participants	8	12
Baseline	148.125	151.083
6 weeks post treatment	106.000	108.273

2. Secondary Outcome

Title	Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL)
Description	12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - [HDL-C + TG/5] after treatment for 6 weeks.
Time Frame	6 weeks post treatment

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Ezetimibe 10 mg	Placebo 10 mg
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.
Measure Participants	8	12
Number [Participants]	7 70%	8 66.7%

3. Secondary Outcome

Title	High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg
Description	12-hour fasting blood samples were collected in participants and the high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol was measured with the basic lipid panel test.
Time Frame	6 weeks post treatment

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Ezetimibe 10 mg	Placebo 10 mg
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.	Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.
Measure Participants	8	12
HDL-C at baseline	53.250	57.667
HDL-C at 6 weeks	52.625	53.500
Total Cholesterol at baseline	219.125	226.000
Total Cholesterol at 6 weeks	156.375	185.667
Triglycerides at baseline	139.500	131.667
Triglycerides at 6 weeks	115.250	120.250

Adverse Events

Arm/Group Title	Ezetimibe 10 mg		Placebo 10 mg
Arm/Group Description	Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.		Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin.
All Cause Mortality
	Ezetimibe 10 mg		Placebo 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ezetimibe 10 mg		Placebo 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/12 (0%)
Cardiac disorders
Cardiac failure congestive	1/10 (10%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Ezetimibe 10 mg		Placebo 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		3/12 (25%)
Gastrointestinal disorders
Nausea	1/10 (10%)		0/12 (0%)
Metabolism and nutrition disorders
Decreased Appetite	0/10 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)		0/12 (0%)
Back pain	0/10 (0%)		1/12 (8.3%)
Musculoskeletal stiffness	0/10 (0%)		1/12 (8.3%)
Myalgia	1/10 (10%)		0/12 (0%)
Nervous system disorders
Headache	1/10 (10%)		0/12 (0%)
Skin and subcutaneous tissue disorders
pruritis	1/10 (10%)		0/12 (0%)

Limitations/Caveats

Protocol deviations may have occurred that resulted in quality issues associated with reporting of the data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The principal investigator (PI) agrees not to publish or publicly present any interim results of the Study without prior written consent of the SPONSOR. The PI further agrees to provide thirty (30) days written notice to the SPONSOR prior to submission for publication or presentation to allow SPONSOR to review abstracts or manuscripts for publication.