Clinical trial NCT04669041: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Study duration per participants is approximatively 16 weeks.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent change in measured LDL-C from baseline (the last available measured LDL-C value obtained up to randomization) to Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Proportion of patients who attain lipid goal (measured LDL-C <2.6 mmol/L [100 mg/dL]) at Week 8
timeFrame: Week 8
measure: Percent change in measured LDL-C plasma level from baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percent change in total cholesterol (TC) from baseline to Week 8
timeFrame: Baseline to Week 8
measure: Percent change in TC from baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percent change in triglyceride (TG) serum levels from baseline to Week 8
timeFrame: Baseline to Week 8
measure: Percent change in TG serum levels from baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percent change in high density lipoprotein cholesterol (HDL-C) from baseline to Week 8
timeFrame: Baseline to Week 8
measure: Percent change in HDL-C from baseline to Week 4
timeFrame: Baseline to Week 4
measure: Number of patients with adverse events (AEs)
timeFrame: Up to 16 weeks (±3 days)
Other outcomes:
Locations:
city: Baotou
country: China
facility: Investigational Site Number :1560033
city: Beijing
country: China
facility: Investigational Site Number :1560001
city: Beijing
country: China
facility: Investigational Site Number :1560068
city: Beijing
country: China
facility: Investigational Site Number :1560021
city: Bengbu
country: China
facility: Investigational Site Number :1560025
city: Changchun
country: China
facility: Investigational Site Number :1560045
city: Changchun
country: China
facility: Investigational Site Number :1560067
city: Changsha
country: China
facility: Investigational Site Number :1560052
city: Chengdu
country: China
facility: Investigational Site Number :1560041
city: Chongqing
country: China
facility: Investigational Site Number :1560060
city: Dalian
country: China
facility: Investigational Site Number :1560015
city: Haikou
country: China
facility: Investigational Site Number :1560029
city: Hohhot
country: China
facility: Investigational Site Number :1560006
city: Hohhot
country: China
facility: Investigational Site Number :1560007
city: Jilin
country: China
facility: Investigational Site Number :1560014
city: Jinan
country: China
facility: Investigational Site Number :1560020
city: Lishui
country: China
facility: Investigational Site Number :1560061
city: Liuzhou
country: China
facility: Investigational Site Number :1560071
city: Nanjing
country: China
facility: Investigational Site Number :1560066
city: Nanning
country: China
facility: Investigational Site Number :1560055
city: Shanghai
country: China
facility: Investigational Site Number :1560027
city: Shenyang
country: China
facility: Investigational Site Number :1560034
city: Siping
country: China
facility: Investigational Site Number :1560010
city: Tianjin
country: China
facility: Investigational Site Number :1560002
city: Tianjin
country: China
facility: Investigational Site Number :1560053
city: Wuhan
country: China
facility: Investigational Site Number :1560047
city: Wuhan
country: China
facility: Investigational Site Number :1560009
city: Wuhan
country: China
facility: Investigational Site Number :1560035
city: Xi'An
country: China
facility: Investigational Site Number :1560022
city: Xi'an
country: China
facility: Investigational Site Number :1560070
city: Xuzhou
country: China
facility: Investigational Site Number :1560003
city: Yangzhou
country: China
facility: Investigational Site Number :1560065
city: Yanji
country: China
facility: Investigational Site Number :1560057
city: Yinchuan
country: China
facility: Investigational Site Number :1560064
city: Yueyang
country: China
facility: Investigational Site Number :1560019
city: Yuncheng
country: China
facility: Investigational Site Number :1560062
city: Zhanjiang
country: China
facility: Investigational Site Number :1560005
city: Zhenjiang
country: China
facility: Investigational Site Number :1560011
city: Zhuzhou
country: China
facility: Investigational Site Number :1560063
city: Zibo
country: China
facility: Investigational Site Number :1560037
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: