A Study to Evaluate the Efficacy and the Safety of Single Pill Combination (SPC) Ezetimibe/Rosuvastatin in Chinese Adult Patients With Primary Hypercholesterolemia Not Adequately Controlled on Statin Therapy

Hypercholesterolemia Clinical Trial

— ROZEL  

Official title:

A Randomized Double-blinded, Double Dummy, Active-controlled, Parallel Design, Phase 3 Clinical Trial to Evaluate the Efficacy and the Safety of Single Pill Combination (SPC) Ezetimibe/Rosuvastatin in Chinese Adult Patients With Primary Hypercholesterolemia, Not Adequately Controlled on Statin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04669041
• Other study ID #: LPS16135
• Secondary ID: U1111-1227-3920
• Status: Completed
• Phase: Phase 3
• Start date: December 8, 2020
• Est. completion date: June 15, 2022

Study information

• Verified date: June 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate the superiority of the single pill combination (SPC) ezetimibe 10 mg/rosuvastatin 10 mg (E10/R10) compared to rosuvastatin 10 mg (R10), in the reduction of low density lipoprotein cholesterol (LDL-C) after 8 weeks.

Secondary Objectives:

• To evaluate the proportion of patients who attain their LDL-C goal.

• To evaluate the effect of SPC (E10/R10) compared to rosuvastatin 10 mg (R10) in reduction of LDL-C at Week 4.

• To evaluate the effect of SPC (E10/R10) compared to R10 on other lipid parameters at Week 4 and Week 8.

• To evaluate the safety of SPC (E10/R10) and R10.

Description:

Study duration per participants is approximatively 16 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: June 15, 2022
• Est. primary completion date: June 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.

• Patients with primary hypercholesterolemia.

• Inclusion criteria in the run-in period: Participants who are not adequately controlled (defined by screening LDL-C >2.6 mmol/L (100 mg/dL) and =4.9 mmol/L (190 mg/dL)with a 10 mg stable daily dose of rosuvastatin, or equipotent statin for 4 weeks prior to the screening visit, without any other lipid modifying therapy (LMT). Inclusion criteria in the randomized double-blind period: Participants who are not adequately controlled based on sample taken at qualifying pre randomization visit, despite stabilized dose of rosuvastatin 10 mg (defined by measured LDL-C =2.6 mmol/L (100 mg/dL) and =4.9 mmol/L (190 mg/dL).

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Capable of giving signed informed consent.

Exclusion criteria:

• Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping).

• Patient who has received LDL-C plasmapheresis treatment within 2 months prior to the screening visit, or has plans to receive it during the study.

• Recently diagnosed (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina, myocardial revascularization (percutaneous coronary intervention [PCI], coronary artery bypass graft surgery [CABG]), transient ischemic attack (TIA), or stroke, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease.

• Planned to undergo scheduled PCI, CABG, carotid or peripheral revascularization during the study.

• Severe hypertension (treated or untreated) with systolic blood pressure (SBP) >160 mm Hg or diastolic blood pressure (DBP) >100 mm Hg at study entry.

• History of severe congestive heart failure (New York Heart Association Class IIIb or IV) within the past 12 months.

• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins, according to Investigator's medical judgement.

• Uncontrolled (as determined by fasting glucose >180 mg/mL or HbA1c >9%) or newly diagnosed (within 3 months of study entry) diabetes mellitus at the screening visit.

• History of cancer within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.

• Conditions/situations such as:

• Patient with a short life expectancy.

• Patient with conditions/concomitant diseases making them non-evaluable for the primary efficacy endpoint, according to Investigator's medical judgement.

• Requirement for concomitant treatment that could bias primary evaluation, according to Investigator's medical judgement.

• Impossibility to meet specific protocol requirements (eg, ability to make study visits).

• Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the study.

• Patient not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures.

• Known history of hypersensitivity reaction to statins and/or ezetimibe.

• Current myopathy.

• A history of statin-induced myopathy or rhabdomyolysis.

• Current active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x upper limit of normal (ULN) range at the screening visit.

• All contraindications to the active comparator (rosuvastatin) and background therapies or warning/precaution of use (when appropriate) as displayed in the respective National Product Labeling.

• Patients not previously instructed on a cholesterol-lowering diet prior to the screening visit.

• Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to screening visit.

• Use of hormone replacement therapy or oral contraceptives unless regimen has been stable in the past 6 weeks prior to the screening visit and no plans to change the regimen during the study.

• Concomitant administration of cyclosporine (at screening and randomization visits).

• Human immunodeficiency virus (HIV) patients receiving protease inhibitors (at screening and randomization visits).

• Patient who has taken any active investigational drugs (E10/R10) within 1 month or 5 half-lives prior to screening, whichever is longer.

• Laboratory findings obtained during the screening visit (V1):

• Fasting serum TGs >400 mg/dL.

• Positive serum pregnancy test.

• Serum creatine kinase >3 times ULN.

• Thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or > ULN.

• Glycated hemoglobin A1c (HbA1c) >9%.

• Estimated glomerular filtration rate <30 mL/min/1.73 m2.

• Alanine aminotransferase or AST >3 x ULN.

• Individuals accommodated in an institution because of regulatory or legal order; prisoners or subjects who are legally institutionalized.

• Any technical/administrative reason (eg, patient homeless) that makes it impossible to enroll/randomize the patient in the study.

• Alcohol abuse according to Investigator's medical judgement.

• Participants are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the ICH-GCP Ordinance E6).

• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.

• Any specific situation during study implementation/course that may rise ethics considerations.

• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Rosuvastatin
Pharmaceutical form:Tablet Route of administration: Oral
• SPC ezetimibe/rosuvastatin
Pharmaceutical form:Tablet Route of administration: Oral
• Rosuvastatin active capsule
Pharmaceutical form:Capsule Route of administration: Oral
• Placebo
Pharmaceutical form:Tablet Route of administration: Oral
• Placebo
Pharmaceutical form:Capsule Route of administration: Oral

Locations

Country	Name	City	State
China	Investigational Site Number :1560033	Baotou
China	Investigational Site Number :1560001	Beijing
China	Investigational Site Number :1560021	Beijing
China	Investigational Site Number :1560068	Beijing
China	Investigational Site Number :1560025	Bengbu
China	Investigational Site Number :1560045	Changchun
China	Investigational Site Number :1560067	Changchun
China	Investigational Site Number :1560052	Changsha
China	Investigational Site Number :1560041	Chengdu
China	Investigational Site Number :1560060	Chongqing
China	Investigational Site Number :1560015	Dalian
China	Investigational Site Number :1560029	Haikou
China	Investigational Site Number :1560006	Hohhot
China	Investigational Site Number :1560007	Hohhot
China	Investigational Site Number :1560014	Jilin
China	Investigational Site Number :1560020	Jinan
China	Investigational Site Number :1560061	Lishui
China	Investigational Site Number :1560071	Liuzhou
China	Investigational Site Number :1560066	Nanjing
China	Investigational Site Number :1560055	Nanning
China	Investigational Site Number :1560027	Shanghai
China	Investigational Site Number :1560034	Shenyang
China	Investigational Site Number :1560010	Siping
China	Investigational Site Number :1560002	Tianjin
China	Investigational Site Number :1560053	Tianjin
China	Investigational Site Number :1560009	Wuhan
China	Investigational Site Number :1560035	Wuhan
China	Investigational Site Number :1560047	Wuhan
China	Investigational Site Number :1560022	Xi'An
China	Investigational Site Number :1560070	Xi'an
China	Investigational Site Number :1560003	Xuzhou
China	Investigational Site Number :1560065	Yangzhou
China	Investigational Site Number :1560057	Yanji
China	Investigational Site Number :1560064	Yinchuan
China	Investigational Site Number :1560019	Yueyang
China	Investigational Site Number :1560062	Yuncheng
China	Investigational Site Number :1560005	Zhanjiang
China	Investigational Site Number :1560011	Zhenjiang
China	Investigational Site Number :1560063	Zhuzhou
China	Investigational Site Number :1560037	Zibo

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in measured LDL-C from baseline (the last available measured LDL-C value obtained up to randomization) to Week 8	The percent change from baseline in measured LDL-C at Week 8 will be analyzed in the modified intent-to-treat (mITT) population using a mixed effect model with repeated measures (MMRM) approach.	Baseline to Week 8
Secondary	Proportion of patients who attain lipid goal (measured LDL-C <2.6 mmol/L [100 mg/dL]) at Week 8		Week 8
Secondary	Percent change in measured LDL-C plasma level from baseline to Week 4		Baseline to Week 4
Secondary	Percent change in total cholesterol (TC) from baseline to Week 8		Baseline to Week 8
Secondary	Percent change in TC from baseline to Week 4		Baseline to Week 4
Secondary	Percent change in triglyceride (TG) serum levels from baseline to Week 8		Baseline to Week 8
Secondary	Percent change in TG serum levels from baseline to Week 4		Baseline to Week 4
Secondary	Percent change in high density lipoprotein cholesterol (HDL-C) from baseline to Week 8		Baseline to Week 8
Secondary	Percent change in HDL-C from baseline to Week 4		Baseline to Week 4
Secondary	Number of patients with adverse events (AEs)		Up to 16 weeks (±3 days)