A 12-week Study to Compare the Efficacy and Safety of Fixed Combinations of Fenofibrate/Simvastatin 145/20mg and Fenofibrate/Simvastatin 145/40mg Tablets Versus Fenofibrate or Simvastatin Monotherapies in Subjects With Abnormal Blood Levels of Fats (Lipids) and at High Risk of Cardiovascular Disease

Dyslipidemia Clinical Trial

Official title:

A 12-week, Double-blind, Randomized Study to Compare the Efficacy and Safety of Fixed Combinations of Fenofibrate / Simvastatin 145/20mg and Fenofibrate / Simvastatin 145/40mg Tablets vs. Matching Monotherapies in Dyslipidemic Subjects at High Risk of Cardiovascular Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01674712
• Other study ID #: M13-377
• Secondary ID: 2011-005924-16
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2012
• Last updated: November 24, 2014
• Start date: June 2012
• Est. completion date: October 2013

Study information

• Verified date: November 2014
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlRomania: National Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsMexico: Federal Commission for Protection Against Health RisksArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

This is a double-blind, randomized study designed to compare the efficacy and safety of two fixed combinations of fenofibrate / simvastatin 145/20 mg and fenofibrate / simvastatin 145/40 mg tablets vs. matching monotherapies in subjects with abnormal fat (lipids) in the blood and at high risk of cardiovascular disease. Fenofibrate is a treatment that lowers fat in blood. It is prescribed in patients with high levels of triglycerides (TG). The drug has been marketed in more than 80 countries since 1975. Simvastatin is also used for the treatment of patients with a high level of cholesterol. These have also been marketed worldwide for more than 20 years. It is important to treat high levels of fats in the blood because it has been shown that even mildly elevated level of lipids in the blood can lead to diseases of the blood vessels. It has been shown in several studies and in clinical practice that the combination of fenofibrate plus simvastatin can lead to improved effects on blood fats, compared to treatment with simvastatin or fenofibrate alone. The main objective of the study is to compare the efficacy of the two fixed-combinations (FC) -fenofibrate/simvastatin 145/20 mg tablet and fenofibrate/simvastatin 145/40 mg tablet in reducing TG and increasing high density lipoprotein cholesterol (HDL-C) versus simvastatin 20 mg or 40 mg, and in reducing low density lipoprotein cholesterol (LDL-C) versus fenofibrate 145 mg.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 575
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Either gender (tentatively 50 percent females to be included and if of childbearing potential she must agree to use medically acceptable methods of contraception from the time of signing the informed consent until 7 days following administration of the last treatment or dose of study medication). Accepted contraceptive methods are implants, injectables, combined oral contraceptives, intra-uterine device or sexual abstinence.

2. between 18 (inclusive) and 80 years

3. With mixed dyslipidemia with fasting lipid results of a blood sample taken at inclusion and after at least 3 months of any statin monotherapy (excluding simvastatin 80 mg, atorvastatin 40 mg and 80 mg, rosuvastatin 20 mg and 40 mg):

• TG higher than/equal to 1.71 mmol/L (higher than/equal to 150 mg/dL) and

• LDL-C higher or equal to 1.81 mmol/L (higher or equal 70 mg/dL) but smaller than/equal to 3.36 mmol/L (smaller than/equal to 130 mg/dL)

4. High risk or very high risk based on known CardioVascular Disease (CVD) or type 2 diabetes or type 1 diabetes with microalbuminuria or a Systematic Coronary Risk Estimation (SCORE) chart risk = 5percent

5. Aspartate aminotransferase and/or alanine aminotransferase smaller than/equal to 2 times the Upper Normal of Limit (UNL)

Exclusion Criteria:

1. Known hypersensitivity to fibrates or simvastatin or known photoallergic or phototoxic reactions under treatment with fibrates or ketoprofen or known allergic reactions caused by peanuts, peanuts or arachis oil or soy lecithin, or related products,

2. Pregnant or lactating women,

3. Unable or unwilling to comply with the protocol and the recommended diet,

4. Likely to withdraw from the study before its completion,

5. Having received an investigational drug or vaccine in the last 30 days before date of inclusion, or still participating in such a trial at Visit 1

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Dyslipidemia
• Dyslipidemias

Intervention

Drug:
• Fixed Combination of Fenofibrate/simvastatin 145/20 mg
Fenofibrate/simvastatin oval biconvex film-coated tablet, 145 mg / 20 mg, once daily, 12 weeks
• Simvastatin 20 mg
Simvastatin generic tablet over-encapsulated, 20 mg, once daily, 12 weeks
• Fenofibrate 145 mg
Fenofibrate, tablet, 145 mg, once daily, 12 weeks
• Fixed Combination of Fenofibrate/simvastatin 145/40 mg
Fenofibrate/simvastatin film-coated tablet 145 mg / 40 mg, once daily, 12 weeks
• Simvastatin 40 mg
simvastatin, generic tablet over-encapsulated, 40 mg, once daily, 12 weeks

Locations

Country	Name	City	State
Argentina	Site Reference ID/Investigator# 77956	Buenos Aires
Argentina	Site Reference ID/Investigator# 77957	Buenos Aires
Argentina	Site Reference ID/Investigator# 77958	Buenos Aires
Argentina	Site Reference ID/Investigator# 77959	Buenos Aires
Argentina	Site Reference ID/Investigator# 77960	Buenos Aires
Argentina	Site Reference ID/Investigator# 77961	Buenos Aires
Argentina	Site Reference ID/Investigator# 77965	Buenos Aires
Argentina	Site Reference ID/Investigator# 77967	Buenos Aires
Argentina	Site Reference ID/Investigator# 77968	Buenos Aires
Argentina	Site Reference ID/Investigator# 77969	Buenos Aires
Argentina	Site Reference ID/Investigator# 77966	Cipolletti - Rio Negro
Argentina	Site Reference ID/Investigator# 77955	Santa Fe
Argentina	Site Reference ID/Investigator# 77962	Santa Fe
Argentina	Site Reference ID/Investigator# 77964	Santa Fe
Argentina	Site Reference ID/Investigator# 77963	Tucuman
Czech Republic	Site reference ID/Investigator # 99617	Benatky nad Jizerou
Czech Republic	Site reference ID/Investigator # 102335	Brno
Czech Republic	Site Reference ID/Investigator# 80097	Brno
Czech Republic	Site Reference ID/Investigator# 80094	Prague 10
Czech Republic	Site Reference ID/Investigator# 80095	Prague 4
Czech Republic	Site Reference ID/Investigator# 80093	Praha 8
Czech Republic	Site Reference ID/Investigator# 80098	Teplice
Czech Republic	Site Reference ID/Investigator# 80096	Usti nad Labem
Czech Republic	Site Reference ID/Investigator# 80099	Znojmo
Germany	Site reference ID/Investigator # 97356	Berlin
Germany	Site reference ID/Investigator # 97357	Berlin
Germany	Site Reference ID/Investigator# 80100	Berlin
Germany	Site Reference ID/Investigator# 90673	Berlin
Germany	Site reference ID/Investigator # 102017	Dortmund
Germany	Site reference ID/Investigator # 99876	Dresden
Germany	Site Reference ID/Investigator# 80102	Dusseldorf
Germany	Site Reference ID/Investigator# 80103	Essen
Germany	Site Reference ID/Investigator# 80104	Essen
Germany	Site Reference ID/Investigator# 80105	Frankfurt
Germany	Site Reference ID/Investigator# 80101	Goch
Germany	Site reference ID/Investigator # 99902	Hamburg
Germany	Site reference ID/Investigator # 102015	Karlsruhe
Germany	Site reference ID/Investigator # 102016	Koeln
Mexico	Site Reference ID/Investigator# 77970	Guadalajara, Jal.
Mexico	Site Reference ID/Investigator# 77972	Mexico D.F.
Mexico	Site Reference ID/Investigator# 77973	Mexico D.F.
Mexico	Site Reference ID/Investigator# 77974	Zapopan
Poland	Site Reference ID/Investigator# 80111	Gdansk
Poland	Site Reference ID/Investigator# 80112	Gdansk
Poland	Site Reference ID/Investigator# 80110	Gdynia
Poland	Site Reference ID/Investigator# 80106	Katowice
Poland	Site Reference ID/Investigator# 80109	Plock
Poland	Site Reference ID/Investigator# 80108	Skierniewice
Poland	Site Reference ID/Investigator# 80107	Warsaw
Romania	Site reference ID/Investigator # 80115	Bucharest
Romania	Site Reference ID/Investigator# 80113	Bucharest
Romania	Site Reference ID/Investigator# 80114	Bucharest
Romania	Site Reference ID/Investigator# 80116	Bucharest
Romania	Site Reference ID/Investigator# 80117	Bucharest
Romania	Site Reference ID/Investigator# 80119	Bucharest
Romania	Site Reference ID/Investigator# 80118	Iasi
Russian Federation	Site Reference ID/Investigator# 80120	Kemerovo
Russian Federation	Site Reference ID/Investigator# 80124	Moscow
Russian Federation	Site Reference ID/Investigator# 80127	Moscow
Russian Federation	Site Reference ID/Investigator# 80135	Moscow
Russian Federation	Site Reference ID/Investigator# 80137	Moscow
Russian Federation	Site Reference ID/Investigator# 80121	Novosibirsk
Russian Federation	Site Reference ID/Investigator# 80122	Novosibirsk
Russian Federation	Site Reference ID/Investigator# 80133	Novosibirsk
Russian Federation	Site reference ID/Investigator # 80126	St. Petersburg
Russian Federation	Site reference ID/Investigator # 80128	St. Petersburg
Russian Federation	Site reference ID/Investigator # 80134	St. Petersburg
Russian Federation	Site Reference ID/Investigator# 80136	St. Petersburg
Russian Federation	Site Reference ID/Investigator# 80125	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

Argentina,  Czech Republic,  Germany,  Mexico,  Poland,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Change of TG (Triglyceride)	Collection and measurement of blood samples.	from baseline to 12 weeks of treatment	No
Primary	Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol)	Collection and measurement of blood samples.	from baseline to 12 weeks of treatment	No
Primary	Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol)	Collection and measurement of blood samples.	from baseline to 12 weeks of treatment	No
Secondary	Percentage of Non-HDL (High Density Lipoprotein)-C From Baseline	Collection and measurement of blood samples	12 weeks	No
Secondary	Percentage of TC (Triglyceride) From Baseline	Collection and measurement of blood samples	12 weeks	No
Secondary	Percentage of Apolipoprotein AI From Baseline	Collection and measurement of blood samples	12 weeks	No
Secondary	Percentage of Apolipoprotein B From Baseline	Collection and measurement of blood samples	12 weeks	No
Secondary	Percentage of High-sensitivity C-reactive Protein (hsCRP) From Baseline	Collection and measurement of blood samples	12 weeks	No
Secondary	Percentage of Subjects Meeting Target Levels of Lipids (According to Very High or High Risk)	Collection and measurement of blood samples	12 weeks	No
Secondary	Adverse Events	Collection and measurement of blood samples	12 weeks	Yes
Secondary	Creatine Kinase (CK)	Collection and measurement of blood samples	12 weeks	Yes
Secondary	Alanine Aminotransferase (ALT)	Collection and measurement of blood samples	12 weeks	Yes
Secondary	Plasma Creatinine	Collection and measurement of blood samples	12 weeks	Yes
Secondary	Total Bilirubin	Collection and measurement of blood samples	12 weeks	Yes
Secondary	Cystatin C	Collection and measurement of blood samples	12 weeks	Yes