Clinical trial NCT01674712: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyslipidemia
Keywords: Fibrates
Dyslipidemia
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2012-08-29
Enrollment: 575
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Change of TG (Triglyceride)
timeFrame: from baseline to 12 weeks of treatment
measure: Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol)
timeFrame: from baseline to 12 weeks of treatment
measure: Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol)
timeFrame: from baseline to 12 weeks of treatment
Secondary outcomes:
measure: Percentage of Non-HDL (High Density Lipoprotein)-C From Baseline
timeFrame: 12 weeks
measure: Percentage of TC (Triglyceride) From Baseline
timeFrame: 12 weeks
measure: Percentage of Apolipoprotein AI From Baseline
timeFrame: 12 weeks
measure: Percentage of Apolipoprotein B From Baseline
timeFrame: 12 weeks
measure: Percentage of High-sensitivity C-reactive Protein (hsCRP) From Baseline
timeFrame: 12 weeks
measure: Percentage of Subjects Meeting Target Levels of Lipids (According to Very High or High Risk)
timeFrame: 12 weeks
measure: Adverse Events
timeFrame: 12 weeks
measure: Creatine Kinase (CK)
timeFrame: 12 weeks
measure: Alanine Aminotransferase (ALT)
timeFrame: 12 weeks
measure: Plasma Creatinine
timeFrame: 12 weeks
measure: Total Bilirubin
timeFrame: 12 weeks
measure: Cystatin C
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77961
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77957
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77958
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77960
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77959
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77969
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77967
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77968
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77965
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 77956
city: Cipolletti - Rio Negro
country: Argentina
facility: Site Reference ID/Investigator# 77966
city: Santa Fe
country: Argentina
facility: Site Reference ID/Investigator# 77955
city: Santa Fe
country: Argentina
facility: Site Reference ID/Investigator# 77962
city: Santa Fe
country: Argentina
facility: Site Reference ID/Investigator# 77964
city: Tucuman
country: Argentina
facility: Site Reference ID/Investigator# 77963
city: Benatky nad Jizerou
country: Czech Republic
facility: Site reference ID/Investigator # 99617
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 80097
city: Brno
country: Czech Republic
facility: Site reference ID/Investigator # 102335
city: Prague 10
country: Czech Republic
facility: Site Reference ID/Investigator# 80094
city: Prague 4
country: Czech Republic
facility: Site Reference ID/Investigator# 80095
city: Praha 8
country: Czech Republic
facility: Site Reference ID/Investigator# 80093
city: Teplice
country: Czech Republic
facility: Site Reference ID/Investigator# 80098
city: Usti nad Labem
country: Czech Republic
facility: Site Reference ID/Investigator# 80096
city: Znojmo
country: Czech Republic
facility: Site Reference ID/Investigator# 80099
city: Berlin
country: Germany
facility: Site reference ID/Investigator # 97356
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 90673
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 80100
city: Berlin
country: Germany
facility: Site reference ID/Investigator # 97357
city: Dortmund
country: Germany
facility: Site reference ID/Investigator # 102017
city: Dresden
country: Germany
facility: Site reference ID/Investigator # 99876
city: Dusseldorf
country: Germany
facility: Site Reference ID/Investigator# 80102
city: Essen
country: Germany
facility: Site Reference ID/Investigator# 80104
city: Essen
country: Germany
facility: Site Reference ID/Investigator# 80103
city: Frankfurt
country: Germany
facility: Site Reference ID/Investigator# 80105
city: Goch
country: Germany
facility: Site Reference ID/Investigator# 80101
city: Hamburg
country: Germany
facility: Site reference ID/Investigator # 99902
city: Karlsruhe
country: Germany
facility: Site reference ID/Investigator # 102015
city: Koeln
country: Germany
facility: Site reference ID/Investigator # 102016
city: Guadalajara, Jal.
country: Mexico
facility: Site Reference ID/Investigator# 77970
city: Mexico D.F.
country: Mexico
facility: Site Reference ID/Investigator# 77973
city: Mexico D.F.
country: Mexico
facility: Site Reference ID/Investigator# 77972
city: Zapopan
country: Mexico
facility: Site Reference ID/Investigator# 77974
city: Gdansk
country: Poland
facility: Site Reference ID/Investigator# 80111
city: Gdansk
country: Poland
facility: Site Reference ID/Investigator# 80112
city: Gdynia
country: Poland
facility: Site Reference ID/Investigator# 80110
city: Katowice
country: Poland
facility: Site Reference ID/Investigator# 80106
city: Plock
country: Poland
facility: Site Reference ID/Investigator# 80109
city: Skierniewice
country: Poland
facility: Site Reference ID/Investigator# 80108
city: Warsaw
country: Poland
facility: Site Reference ID/Investigator# 80107
city: Bucharest
country: Romania
facility: Site reference ID/Investigator # 80115
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 80114
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 80117
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 80116
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 80119
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 80113
city: Iasi
country: Romania
facility: Site Reference ID/Investigator# 80118
city: Kemerovo
country: Russian Federation
facility: Site Reference ID/Investigator# 80120
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 80135
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 80137
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 80124
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 80127
city: Novosibirsk
country: Russian Federation
facility: Site Reference ID/Investigator# 80122
city: Novosibirsk
country: Russian Federation
facility: Site Reference ID/Investigator# 80121
city: Novosibirsk
country: Russian Federation
facility: Site Reference ID/Investigator# 80133
city: St. Petersburg
country: Russian Federation
facility: Site reference ID/Investigator # 80134
city: St. Petersburg
country: Russian Federation
facility: Site reference ID/Investigator # 80126
city: St. Petersburg
country: Russian Federation
facility: Site reference ID/Investigator # 80128
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 80136
city: Yaroslavl
country: Russian Federation
facility: Site Reference ID/Investigator# 80125
Study officials:
affiliation: Abbott
name: Jean-Claude Ansquer, MD
role: STUDY_DIRECTOR
References: