Efficacy and Safety of Atorvastatin + Perindopril Fixed-Dose Combination S05167 in Adult Patients With Arterial Hypertension and Dyslipidemia

Efficacy and Safety of Atorvastatin + Perindopril Fixed-Dose Combination S05167 in Adult Patients With Arterial Hypertension and Dyslipidemia, 8 Weeks, Phase 3, Randomized, Double-blind, Active-control, Multinational, Multi-center, Parallel Study

The purpose of this study is to demonstrate the superiority of atorvastatin/perindopril fixed dose combination (FDC) S05167 as compared to atorvastatin reference drug alone or perindopril drug alone on systolic blood pressure decrease and LDL cholesterol decrease respectively in patients presenting with hypertension and dyslipidemia after 8 weeks of treatment.

Study Overview

• Status: Terminated
• Conditions: Hypertension; Dyslipidemias
• Intervention / Treatment: Drug: Atorvastatin/Perindopril; Drug: Atorvastatin; Drug: Perindopril

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• Georgia
  • Kutaisi, Georgia, 46000
    • LTD "Clinic-LJ"
  • Marneuli, Georgia, 3000
    • LTD "Marnecore"
  • Tbilisi, Georgia, 01102
    • "Aleksandre Aladashvili Clinic" LLC
  • Tbilisi, Georgia, 01112
    • Israel-Georgian Medical Research Clinic "Helsicore"
  • Tbilisi, Georgia, 0159
    • Bokhua Memorial Cardiovascular Center
  • Tbilisi, Georgia, 0159
    • Ltd "Digomi Medical Center"
  • Tbilisi, Georgia, 0160
    • LTD "MediClubGeorgia"
  • Tbilisi, Georgia, 0179
    • Emergency Cardiology Center n.a. Acad G Chapidze
• Russian Federation
  • Arkhangel'sk, Russian Federation, 163000
    • FSI "Northern Medical Clinical Centre n.a. N.A. Semashko FMBA of Russia"
  • Arkhangel'sk, Russian Federation, 163001
    • Сity clinical hospital #1 named after E.E.Volosevich
  • Chelyabinsk, Russian Federation, 454092
    • Non-State Institution of Healthcare "Railway Clinical Hospital at station Chelyabinsk of open joint-stock company "Russian Railways"
  • Moscow, Russian Federation, 101990
    • Federal State Institution "National Medical Research Center for Preventive Medicine" of the Ministry of Healthcare of the Russian Federation
  • Moscow, Russian Federation, 121309
    • State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital #51" of Department of Healthcare of Moscow
  • Moscow, Russian Federation, 120016
    • State Budgetary Institution of Healthcare of the City of Moscow "City Clinical Hospital No. 17 of the Department of Healthcare of the City of Moscow"
  • Orenburg, Russian Federation, 460040
    • "Orenburg State Medical University" based on Municipal State healthcare Institution "City Hospital emergency # 1" of the city of Orenburg
  • Penza, Russian Federation, 440026
    • SBHI "Penza Regional Clinical Hospital n.a. N.N. Burdenko"
  • Ryazan', Russian Federation, 390039
    • State budgetary institution "Ryazan' regional clinical hospital"
  • Saint Petersburg, Russian Federation, 192289
    • Saint Petersburg state budgetary institution of healthcare "City policlinic #109"
  • Saint Petersburg, Russian Federation, 195067
    • GBOU VPO "North-Western State Medical University named after I.I. Mechnikov" , the department faculty and hospital care, court number 5
  • Saint Petersburg, Russian Federation, 196084
    • Medical Research Institute, LLC
  • Saint Petersburg, Russian Federation, 196600
    • SPB SBHI "City Hospital # 38 n.a. N.A. Semashko"
  • Saint Petersburg, Russian Federation, 197706
    • Saint-Petersburg GUZ "City Hospital #40 of the Resort District"
  • Saint Petersburg, Russian Federation, 198205
    • St. Petersburg State Institution of Health "City Hospital № 15" Cardiology Care Unit
  • Saint Petersburg, Russian Federation, 198260
    • St. Petersburg State Budgetary Institution of Healthcare "Diagnostic center #85"
  • Saint Petersburg, Russian Federation, 199106
    • SPB SBHI "Pokrovskaya City Hospital"
  • Saint Petersburg, Russian Federation, 199178
    • LLC "MART" Sankt Petersburg
  • Saratov, Russian Federation, 410028
    • Saratov Research Cardiology Institute of Roszdrav
  • Tver, Russian Federation, 166036
    • State Budgetary institutionof heath of Tver region "Region clinical hospital"
  • Vladimir, Russian Federation, 600020
    • State Institution of Healthcare Vladimir region ''City Hospital № 4 of Vladimir "
  • Yaroslavl, Russian Federation, 150062
    • State Budgetary institution of heath of Yaroslavl region "Regional clinical hospital"
• Ukraine
  • Ivano-Frankivs'k, Ukraine, 76018
    • State Higher Educational Institution "Ivano-Frankivsk National Medical University", Chair of Internal Medicine #2 and Nursing based on Communal Institution Ivano-Frankivsk Regional Clinical Cardiological Center, Chronic Ischaemic Heart Disease Department
  • Ivano-Frankivs'k, Ukraine
    • Ivano-Frankivsk central city clinical hospital, Cardiology department
  • Kharkiv, Ukraine
    • "L.T. Malaya Therapy National Institute of the National Institute of Medical Science of Ukraine" Department of aging and prevention of metabolic-associated diseases
  • Kharkiv, Ukraine
    • The Training and Research Medical Complex "The University Clinic" of the Kharkiv National Medical University, Department of Therapy, National Pharmaceutical University, Chair of Pharmacotherapy
  • Kiev, Ukraine, 04114
    • State Institution "Institute of gerontology named after D.F. Chebotaryov НAMS of Ukraine, Department of Clinical and Epidemiological Cardiology
  • Kyiv, Ukraine
    • Medical center ''CONSILIUM MEDICAL''
  • Lviv, Ukraine, 79059
    • Danylo Halytskyi Lviv National Medical University Department of Therapy No. 1 and Medical Diagnostics of the Faculty of Postgraduate Education
  • Lviv, Ukraine
    • Chair of Propedeutic of Internal Medicine #1 of Danylo Halytsky Lviv National Medical University based Municipal Non-profit Enterprise "Lviv City Clinical Hospital #5" Out-patient department.
  • Odesa, Ukraine
    • The Medical and Diagnostic Center of LLC "House of Medicine"
  • Ternopil', Ukraine
    • Chair of Internal Medicine #3 of Ternopil National Medical University named after I. Gorbachevsky of MOH of Ukraine based on Outpatient Department of Municipal Institution of Ternopil Regional Council "Ternopil University Hospital",
  • Ternopil', Ukraine
    • Communal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council, Department of Rheumatology, I. Horbachevsky Ternopil National Medical University of MOH of Ukraine, Chair of Internal Medicine #2
  • Vinnytsya, Ukraine
    • Municipal Non-profit Institution "Vinnytsya City Clinical Hospital #1", Therapeutical department; National Pirogov Memorial University, Vinnytsya, Chair of Propedeutics of Internal Medicine;
  • Vinnytsya, Ukraine
    • Private Small-Scale Enterprise Medical Center "Pulse"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men or women from 18 to 79 years old who can comply with the study requirements and timetable,

2. Patients diagnosed with Essential hypertension (as documented in patient's medical file). The diagnosis of hypertension should be based on at least two BP measurements on at least two visits.

   Uncontrolled hypertensive patients currently under monotherapy treatment within at least 4 weeks (except patients treated by perindopril) for combined systolic and diastolic hypertension (140 mmHg ≤ SBP < 160 mmHg and 90 mmHg ≤ DBP < 100 mmHg).

   or Hypertensive patients naïve of treatment with 150 mmHg ≤ SBP <160 mmHg and 90 mmHg ≤ DBP < 100 mmHg.

3. Dysplipidemic patients: naïve of treatment or uncontrolled with statin at lowest dose within at least 4 weeks with 110 mg/ Decilitre (dL) (or 2.84 millimole [mmol] /L) ≤ LDL-c < 190 mg/dL (or 4.91 mmol/L) according to a previous laboratory result within 12 months.

Exclusion Criteria:

1. Unlikely to cooperate in the study,
2. Pregnant and lactating women,

4. Participation in another study at the same time or having participated in another study within 3 months before selection participation in noninterventional registries or epidemiological studies is allowed,

6.Patients treated with >1 anti-hypertensive drug or >1 Lipid lowering drug,

7.Patients previously treated with atorvastatin and/or perindopril,

8.Known resistance to ACE inhibitors,

9.Patients treated with beta-blockers or alpha-blockers,

10. Patients with liver disease or renal impairment,

11.Certain known cardiovascular diseases or cardiac rhythm disorders,

12.Known or suspected symptomatic orthostatic hypotension,

13.Familial hypercholesterolemia,

14.Secondary hypertension or dyslipidemia,

15.Patients who are hypersensitive to atorvastatin, perindopril or to any of the excipients of study drugs,

16.Hypersensitivity to any other ACE inhibitor,

17.History of angioedema associated with previous ACE inhibitor therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S05167	Drug: Atorvastatin/Perindopril; 1 over-encapsulated S05167 capsule, fixed dose combination of Atorvastatin/Perindopril Arginine 40/10 mg, will be administered once daily each day before breakfast during 8 weeks.
Active Comparator: Lipitor®	Drug: Atorvastatin; 1 over-encapsulated atorvastatin 40 mg tablet will be administered once daily each day before breakfast during 8 weeks.
Active Comparator: Coversyl®	Drug: Perindopril; 1 over-encapsulated perindopril 10 mg tablet will be administered once daily each day before breakfast during 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure (SBP)	Mean change from baseline in sitting systolic blood pressure (SBP) in the S05167 group as compared with the Lipitor group (in terms of superiority)	Over 8 weeks
Low-Density Lipoprotein Cholesterol (LDLc)	Percent of change from baseline in Low-Density Lipoprotein Cholesterol (LDLc) in the S05167 group as compared with the Coversyl group (in terms of superiority)	Over 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure (SBP)	Mean change from baseline in sitting systolic blood pressure (SBP) in the S05167 group as compared with Coversyl group	Over 8 weeks
Density Lipoprotein Cholesterol (LDLc)	Percent of change from baseline in Low-Density Lipoprotein Cholesterol (LDLc) level in the S05167 group as compared with the Lipitor group	Over 8 weeks
Diastolic blood pressure (DBP)	Mean change from baseline in diastolic blood pressure (DBP) in each group	Over 8 weeks
Pulse Pressure	Mean change from baseline Pulse Pressure in each group	Over 8 weeks
Lipid parameters	Percent of Change from baseline	Over 8 weeks
Blood pressure response	Percent of responders (in terms of blood pressure response defined by patients with BP< 140/90 mm Hg or SBP decrease > = 20 mm Hg or DBP decrease > =10 mm Hg)	Over 8 weeks
Blood pressure control	Percent of blood pressure control: BP< 140/80 mm Hg AND % of blood pressure control: BP < 130/80 mm Hg	Over 8 weeks
Lipids control	Percent of responders (in terms of lipids control: an absolute reduction to an LDLc level< 2.6 mmol/L [100 mg/dL] or a reduction at least 50%	Over 8 weeks
Adverse events and Serious adverse events (SAE)	Emergent Adverse events and Serious adverse events (SAE)	Over 8 weeks
Vital signs	Blood pressure (BP)	Over 8 weeks
Vital signs	Pulse rate (PR)	Over 8 weeks
Vital signs	Respiratory rate (RR)	Over 8 weeks
Electrocardiogram	Significant abnormalities observed from ECG	Over 8 weeks
Clinical lab tests	Relevant deviations of laboratory test results	Over 8 weeks

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company

Publications and helpful links

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Actual): April 8, 2022
• Study Completion (Actual): April 8, 2022

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 12, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Dyslipidemia; Hypertension; HMG-CoA reductase inhibitor; Cardiovascular; Atorvastatin; Perindopril; ACE inhibitor; Fixed combination
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hypertension; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Atorvastatin; Perindopril
• Other Study ID Numbers: CL3-05167-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. [study-level clinical trial data]

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No