Efficacy/Safety of Rosuvastatin+Ezetimibe in High Risk Patients With Primary Hypercholesterolemia/Mixed Dyslipidemia

NCT01420549 | Completed Phase 3 Results

• 1 other identifier: ACH-TRZ-03(06/11)
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine the non-inferiority between two different FDC (fixed-dose combination), measuring LDL-Cholesterol levels, in high risk patients with primary hypercholesterolemia or mixed dyslipidemia.

Conditions

Hypercholesterolemia; Dyslipidemia

Keywords

Hypercholesterolemia; Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• Reduction of LDL Cholesterol Levels

  The primary efficacy variable was the percentage of LDL-C variation at the end of nine weeks of treatment, compared to baseline (pre-randomization), in participants who achieved LDL \<100 mg/dL were considered to have been successfully treated.

  Baseline compared to the end of 9 weeks of treatment

Study Arms (2)

Rosuvastatin + Ezetimibe

EXPERIMENTAL

Participants received Rosuvastatin 10 mg+ Ezetimibe 10 mg tablet orally once daily for 5 weeks and after a LDL evaluation if it level was \<100 mg/dL the dose was maintained for more 4 weeks. However, if the LDL-C levels was ≥100 mg/dL, the dose was adjusted to Rosuvastatin 20 mg+ Ezetimibe 10mg tablet orally once daily for more 4 weeks.

Drug: Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation.

Simvastatin + Ezetimibe

ACTIVE COMPARATOR

Participants received Simvastatin 20 mg+ Ezetimibe 10 mg tablet orally once daily for 5 weeks and after a LDL evaluation if it level was \<100 mg/dL the dose was maintained for more 4 weeks. However, if the LDL-C levels was ≥100 mg/dL, the dose was adjusted to Simvastatin 40 mg + Ezetimibe 10mg tablet orally once daily for more 4 weeks.

Drug: Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation.

Interventions

Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation. DRUG

Tables containing: Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according to clinical evaluation.

Also known as: Lance

Rosuvastatin + Ezetimibe

Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation. DRUG

Tables containing: Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according to clinical evaluation.

Also known as: Vytorin

Simvastatin + Ezetimibe

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants aged 18 to 80 years;
• Participants diagnosed with primary hypercholesterolemia or mixed dyslipidemia;
• Participants must not have other clinically significant comorbidities that may interfere with study evaluations;
• Participants able to understand and adhere to the therapeutic scheme and to attend the study visits;
• Participants who agree to maintain a low cholesterol diet throughout the study;
• Participants who agree to discontinue previous medication for hypercholesterolemia treatment throughout the study;
• Participants with hypercholesterolemia or mixed dyslipidemia with the following laboratory test results on the baseline visit: LDL-C level \>130 mg/dl if were receiving prior treatment with statins; or LDL-C level \>100 mg/dl if were receiving prior treatment with first generation statins; or LDL ≥160 mg/dL and ≤220 mg/dL and triglycerides ≤350 mg/dL if were not in prior treatment with statins.
• Female participants in reproductive age with negative serum beta-hCG test result in the baseline visit who agree to use acceptable contraceptive methods (oral contraceptives, injectable contraceptives, intrauterine device (IUD), hormonal implants, barrier methods, hormonal patch, tubal ligation or female participants who declare to perform non reproductive sexual practices); except surgically sterile (for example oophorectomy and hysterectomy), surgical sterilization or of the partner; or postmenopausal for at least one year;
• Participants with laboratorial test results after treatment with Simvastatin 20 mg for four weeks with LDL-C level ≥100 mg/dl.

You may not qualify if:

• Heart failure class III or IV (NYHA- New York Heart Association);
• Blood dyscrasia;
• Unstable angina pectoris;
• Myocardial infarction in the last 3 months;
• Planning for CABG (coronary artery bypass graft), peripheral or carotid percutaneous intervention for the next 90 days;
• Renal insufficiency: estimated Glomerular Filtration Rate (GFR) \< 30 ml/min/m2;
• History of alcoholism that, at the investigator's discretion, could compromise the drug treatment compliance;
• Participants with comorbidities that hinder the interpretation of results or contraindicate the lipid-lowering therapy \[uncontrolled hypothyroidism (thyroid-stimulating hormone \[TSH\] \> 8 mUI/mL); uncontrolled diabetes (Hemoglobin A1c \[HbA1c\] \> 8%); active hepatic disease; antiretroviral therapy for HIV, neoplasm (except for adequately treated skin cancer within the past 5 years), concomitant immunosuppressive therapy (transplant receivers and rheumatic disease);
• Uncontrolled systemic arterial hypertension;
• Hypersensitivity to any component of the investigational product;
• Participant who has participated in clinical trial protocols in the last twelve (12) months (CNS Resolution 251 of August 7, 1997, Part III, sub-item J), unless the investigator considers that there may be a direct benefit to the patient;
• Any observational finding (clinical/ physical evaluation), laboratory abnormality, disease or therapy that is interpreted by the investigator as a risk to the research participant's participation in the clinical trial;
• Aspartate transaminase (AST) or alanine aminotransferase (ALT) more than two times the normal upper limit of the central laboratory reference range after treatment with Simvastatin 20 mg for four weeks;
• Creatine phosphokinase (CPK) more than three times the normal upper limit of the central laboratory reference range after treatment with Simvastatin 20 mg for four weeks.

Sponsors & Collaborators

• Ache Laboratorios Farmaceuticos S.A.: lead

Study Sites (7)

Centro de Pesquisas em Diabetes e Doenças Endócrino-Metabólicas- UFC

Fortaleza, Ceará, Brazil

Location

Centro de Pesquisas Médicas Básica e Clínica

Recife, Pernambuco, Brazil

Location

CCBR Brasil Centro de Pesquisas e Análises Clínicas

Rio de Janeiro, Brazil

Location

CEPIC Centro Paulista de Investigação Clínica

São Paulo, Brazil

Location

FGM - Clínica Paulista de Doenças Cardiovasculares

São Paulo, Brazil

Location

Hospital do Rim e Hipertensão

São Paulo, Brazil

Location

Universidade Federal de São Paulo

São Paulo, Brazil

Location

Related Publications (1)

• Vattimo ACA, Fonseca FAH, Morais DC, Generoso LF, Herrera R, Barbosa CM, de Oliveira Izar MC, Cardoso RA, Zung S. Efficacy and Tolerability of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Compared with a Fixed-Dose Combination of Simvastatin and Ezetimibe in Brazilian Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia: A Multicenter, Randomized Trial. Curr Ther Res Clin Exp. 2020 Jul 28;93:100595. doi: 10.1016/j.curtheres.2020.100595. eCollection 2020.

  PMID: 32904162 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Dyslipidemias

Interventions

Rosuvastatin Calcium; Ezetimibe; Simvastatin; Ezetimibe, Simvastatin Drug Combination

Condition Hierarchy (Ancestors)

Hyperlipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azetidines; Azetines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Antonio Carlos Amedeo Vattimo
• Organization: Aché Laboratórios Farmacêuticos S. A.

antonio.vattimo@ache.com.br

+55 11 26088111

Study Officials

• Francisco Fonseca, physician

  Universidade Federal de São Paulo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: August 19, 2011
• Study Start: March 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 22, 2020
• Results First Posted: January 22, 2020

Record last verified: 2020-01

Locations

BR (7)