HypercholesterolemiaPhase 3NCT01370603

A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1)

A Phase 3 study testing Atorvastatin, Ezetimibe and Ezetimibe/atorvastatin in people with Hypercholesterolemia, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine whether ezetimibe/atorvastatin 10 mg/40 mg combination tablet is equivalent to the coadministration of ezetimibe 10 mg and atorvastatin 40 mg in lowering low-density-lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment. Read more about this study

Who is it for?: Ages 18 to 79 years
Conditions the study is for: Hypercholesterolemia
What is being tested?: Atorvastatin, Ezetimibe and Ezetimibe/atorvastatin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 328 participants
Where: No sites listed yet
Study dates: Sep 2011to May 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

At low, moderate, or moderately high cardiovascular risk (according to National Cholesterol Education Program adult treatment panel III [NCEP ATP III] guidelines) and either statin-naïve with LDL-C ≥130 mg/dL for low risk or ≥100 mg/dL for moderate or moderately high risk OR on an allowable statin with on-therapy LDL-C ≥100 mg/dL in acceptable range and can safely discontinue and switch to study medication.
Is willing to maintain a cholesterol-lowering diet throughout the study.
Female of reproductive potential agrees to remain abstinent or to use (or have their partner use) 2 acceptable methods of birth control throughout the study.
Female receiving non-cyclical hormone therapy, if maintained on a stable dose and regimen for at least 8 weeks prior to the study and if willing to continue the same regimen throughout the study.
Off-therapy LDL-C levels are: for low risk patients, ≥130 mg/dL and ≤300 mg/dL; for moderate risk patients, ≥100 mg/dL and ≤300 mg/dL; for moderately high risk patients, ≥100 mg/dL and ≤275 mg/dL.
Has liver transaminases ≤2 X upper limit of normal (ULN) with no active liver disease.
Has creatine kinase (CK) levels ≤3 X ULN.
Has triglyceride (TG) concentrations ≤400 mg/dL.

Who cannot join

Hypersensitivity or intolerance to ezetimibe, atorvastatin, the ezetimibe/atorvastatin combination tablet, or any component of these medications, or a history of myopathy or rhabdomyolysis with ezetimibe or any statin.
Routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week).
Is pregnant or lactating.
Has been treated with any other investigational drug within 30 days of the study.
Is high risk (according to NCEP ATP III guidelines), including but not limited to one or more of the following: diabetes mellitus (Type I or II), myocardial infarction, coronary artery bypass surgery, angioplasty, stable or unstable angina.
Has any of the following medical conditions: congestive heart failure; uncontrolled cardiac arrhythmias or recent significant changes in an electrocardiogram (ECG); homozygous familial hypercholesterolemia or has undergone LDL apheresis; partial ileal bypass, gastric bypass, or other significant intestinal malabsorption; uncontrolled hypertension; kidney disease; disease known to influence serum lipids or lipoproteins; hematologic, digestive, or central nervous system disorder; known to be human immunodeficiency virus (HIV) positive; history of malignancy ≤5 years prior to the study, except for adequately treated basal cell or squamous cell skin cancer or in situ
cervical cancer; mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
Taking prohibited medications/foods including: systemic azole antifungals (e.g., fluconazole, ketoconazole), erythromycin or clarithromycin, and cyclosporine; ritonavir and saquinavir or lopinavir; >5 cups of grapefruit juice per day; combination therapies of ezetimibe + atorvastatin (10/80 mg) or ezetimibe + rosuvastatin (10/20 mg or 10/40 mg); non-statin lipid-lowering agents including fish oils containing >900 mg/day of eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA), red yeast extract, Cholestin™, bile acid sequestrants, other cholesterol-lowering agents, niacin (>200 mg/day), or fibrates; systemic corticosteroids; psyllium, other fiber-based laxatives, phytosterol margarines, and/or over the counter (OTC) therapies known to affect serum lipid levels; orlistat or other anti-obesity medications and not maintained on a stable dose; any cyclical hormones; warfarin treatment without a stable dose or a stable International Normalized Ratio (INR).

About this study

Official title: A Randomized, Double-Blind, Active-Controlled, Multicenter, Crossover Study to Evaluate the Efficacy of Ezetimibe/Atorvastatin 10 mg/40 mg Fixed-Dose Combination Tablet Compared to Co-Administration of Marketed Ezetimibe 10 mg and Atorvastatin 40 mg in Patients With Primary Hypercholesterolemia

Conditions: Hypercholesterolemia
Being tested: Atorvastatin, Ezetimibe, Ezetimibe/atorvastatin, Placebo to atorvastatin, Placebo to ezetimibe
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AtorvastatinDrug
Also called Lipitor®
40 mg tablet administered orally once daily
EzetimibeDrug
Also called Zetia®
10 mg tablet administered orally once daily
Ezetimibe/atorvastatinDrug
Also called Liptruzet®, MK-0653C
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet administered orally once daily
Placebo to atorvastatinDrug
Administered orally once daily
Placebo to ezetimibeDrug
Administered orally once daily
Placebo to ezetimibe/atorvastatinDrug
Administered orally once daily

Study groups in NCT01370603
Study group	Role	What they receive
Ezetimibe and atorvastatin	Active comparator	Medication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including 10 mg ezetimibe, 40 mg atorvastatin, and placebo to ezetimibe/atorvastatin. Receives: Drug: Atorvastatin; Drug: Ezetimibe; Drug: Placebo to ezetimibe/atorvastatin
Ezetimibe/atorvastatin combination	Experimental	Medication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including ezetimibe/atorvastatin 10 mg/40 mg, placebo to ezetimibe, and placebo to atorvastatin. Receives: Drug: Ezetimibe/atorvastatin; Drug: Placebo to atorvastatin; Drug: Placebo to ezetimibe

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment
Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6

Secondary outcomes (5)

Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment
Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment
Serum HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment
Non-HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6
Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment
Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6
Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment
Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Measured: Baseline and Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011May 2012

First posted10 Jun 2011 (estimated)
Study startSep 2011
Primary completionMay 2012
Study completionMay 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 328 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01370603
Sponsor's protocol ID: 0653C-190
Status last verified: Feb 2022
First submitted: 8 Jun 2011
Last updated: 9 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Bays HE, Chen E, Tomassini JE, McPeters G, Polis AB, Triscari J. Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model. Fundam Clin Pharmacol. 2015 Apr;29(2):209-18. doi: 10.1111/fcp.12096. Epub 2015 Feb 27.
PubMed 25431239

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

All Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Active-Controlled, Multicenter, Crossover Study to Evaluate the Efficacy of Ezetimibe/Atorvastatin 10 mg/40 mg Fixed-Dose Combination Tablet Compared to Co-Administration of Marketed Ezetimibe 10 mg and Atorvastatin 40 mg in Patients With Primary Hypercholesterolemia
ClinicalTrials.gov ID: NCT01370603
Acronym / sponsor ID: 0653C-190
Conditions: Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 328 participants (actual)
Lead sponsor: Organon and CoIndustry (pharma, biotech, devices)
Study start: Sep 2011
Primary completion: May 2012 (actual)
Study completion: May 2012 (actual)
First posted: 10 Jun 2011 (estimated)
Results: Posted 10 Jul 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Ezetimibe and atorvastatin	Active comparator	Drug: Atorvastatin, Drug: Ezetimibe, Drug: Placebo to ezetimibe/atorvastatinMedication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including 10 mg ezetimibe, 40 mg atorvastatin, and placebo to ezetimibe/atorvastatin.
Ezetimibe/atorvastatin combination	Experimental	Drug: Ezetimibe/atorvastatin, Drug: Placebo to atorvastatin, Drug: Placebo to ezetimibeMedication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including ezetimibe/atorvastatin 10 mg/40 mg, placebo to ezetimibe, and placebo to atorvastatin.

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

At low, moderate, or moderately high cardiovascular risk (according to National Cholesterol Education Program adult treatment panel III [NCEP ATP III] guidelines) and either statin-naïve with LDL-C ≥130 mg/dL for low risk or ≥100 mg/dL for moderate or moderately high risk OR on an allowable statin with on-therapy LDL-C ≥100 mg/dL in acceptable range and can safely discontinue and switch to study medication.
Is willing to maintain a cholesterol-lowering diet throughout the study.
Female of reproductive potential agrees to remain abstinent or to use (or have their partner use) 2 acceptable methods of birth control throughout the study.
Female receiving non-cyclical hormone therapy, if maintained on a stable dose and regimen for at least 8 weeks prior to the study and if willing to continue the same regimen throughout the study.
Off-therapy LDL-C levels are: for low risk patients, ≥130 mg/dL and ≤300 mg/dL; for moderate risk patients, ≥100 mg/dL and ≤300 mg/dL; for moderately high risk patients, ≥100 mg/dL and ≤275 mg/dL.

Key exclusion criteria (8 listed)

Hypersensitivity or intolerance to ezetimibe, atorvastatin, the ezetimibe/atorvastatin combination tablet, or any component of these medications, or a history of myopathy or rhabdomyolysis with ezetimibe or any statin.
Routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week).
Is pregnant or lactating.
Has been treated with any other investigational drug within 30 days of the study.
Is high risk (according to NCEP ATP III guidelines), including but not limited to one or more of the following: diabetes mellitus (Type I or II), myocardial infarction, coronary artery bypass surgery, angioplasty, stable or unstable angina.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AtorvastatinAlso: Lipitor®40 mg tablet administered orally once daily	Drug	Ezetimibe and atorvastatin
EzetimibeAlso: Zetia®10 mg tablet administered orally once daily	Drug	Ezetimibe and atorvastatin
Ezetimibe/atorvastatinAlso: Liptruzet®, MK-0653CEzetimibe/atorvastatin 10 mg/40 mg combination tablet administered orally once daily	Drug	Ezetimibe/atorvastatin combination
Placebo to atorvastatinAdministered orally once daily	Drug	Ezetimibe/atorvastatin combination
Placebo to ezetimibeAdministered orally once daily	Drug	Ezetimibe/atorvastatin combination
Placebo to ezetimibe/atorvastatinAdministered orally once daily	Drug	Ezetimibe and atorvastatin

Primary outcome

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment
Time frame: Baseline and Week 6
Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

5 secondary outcomes

Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment
Time frame: Baseline and Week 6
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment
Time frame: Baseline and Week 6
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment
Time frame: Baseline and Week 6
Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment
Time frame: Baseline and Week 6
Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment
Time frame: Baseline and Week 6

Results and safety

Results posted to the registry on 10 Jul 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Co-administration/Combination Sequence	164	150
Combination/Co-administration Sequence	164	154

Primary outcome: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment

Time frame: Baseline and Week 6. Least squares mean (95% Confidence Interval). Unit: Percentage Change

Measure	Ezetimibe/Atorvastatin Fixed Dose Combination n = 280	Co-Administration Ezetimibe and Atorvastatin n = 280
Value	-58.9 (-60.9 to -56.9)	-58.7 (-60.7 to -56.7)

Ezetimibe/Atorvastatin Fixed Dose Combination vs Co-Administration Ezetimibe and Atorvastatin: Difference in Least-squares means: -0.2 (97.5% CI -1.9 to 1.4), ANCOVA

Population analysed: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 18 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ezetimibe/Atorvastatin Fixed Dose Combination	3 of 303 (1%)	0 of 303 (0%)	Not reported
Co-Administration Ezetimibe and Atorvastatin	2 of 313 (0.6%)	0 of 313 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25431239Bays HE, Chen E, Tomassini JE, McPeters G, Polis AB, Triscari J. Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model. Fundam Clin Pharmacol. 2015 Apr;29(2):209-18. doi: 10.1111/fcp.12096. Epub 2015 Feb 27.

Related trials for Hypercholesterolemia

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atorvastatin, Ezetimibe and Ezetimibe/atorvastatin in people with Hypercholesterolemia, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment (time frame: Baseline and Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01370603, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2022.