Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes

Atherosclerosis Clinical Trial

Official title:

A Phase III, 18 Month, Multicenter, Randomized, Double-Blind, Active-Controlled Clinical Trial to Compare Rosiglitazone Versus Glipizide on the Progression of Atherosclerosis in Subjects With Type 2 Diabetes Mellitus and Cardiovascular Disease (APPROACH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00116831
• Other study ID #: AVD100521
• Status: Completed
• Phase: Phase 3
• First received: June 30, 2005
• Last updated: March 21, 2017
• Start date: January 2005
• Est. completion date: August 2008

Study information

• Verified date: March 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the safety and effectiveness of rosiglitazone against a sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels of the heart.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 672
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion criteria:

• Male or female between 30 to 80 years of age, inclusive.

• Established diagnosis of T2DM (based on diagnostic criteria of the American Diabetes Association (ADA), WHO guidelines or local national guidelines).

• Subjects who are undergoing coronary angiography for evaluation of suspected or previously diagnosed coronary artery disease or who are undergoing PCI.

• Subjects' prior anti-hyperglycemic diabetic therapy:

Diet and exercise only (drug naïve), with HbA1c >7.0 and £ 10.0%. HbA1c > 6.5 and <= 8.5%.

• Left ventricular ejection fraction (EF) ³ 40% as assessed by contrast ventriculography (or previously documented in medical notes within one month prior to index procedure by other methods e.g. echocardiography or nuclear study)

• Female subjects must be postmenopausal (i.e., >6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, Norplant, Depo-Provera, an intra-uterine device (IUD), a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1a, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study medication.

• Willingness and ability to give informed consent prior to entering the study and available to complete the study.

Exclusion Criteria:

• Type 1 diabetes and/or history of diabetic ketoacidosis.

• Exposure to a TZD or other PPAR-g agonist within the 6 months prior to screening visit.

• Subjects treated with triple OAD therapy or high dose dual combination OAD therapy [1].

• Subjects who have required chronic insulin use in the last 6 months (except during pregnancy or acute episodes such as hospitalization, trauma or infection).

• ST segment elevation myocardial infarction in the last 30 days.

• Subjects who have a history or are scheduled to receive coronary artery bypass graft surgery (CABG), valve repair or replacement, aneurysmectomy or planned major non-cardiac surgery during the study period.

• Subjects who have severe cardiac valvular disease

• Stroke or resuscitated in the past 6 months

• History of congestive heart failure (NYHA class I - IV)

• History of significant hypersensitivity or reaction (e.g., difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to any TZD, SU, biguanide or insulin

• Prior history of severe edema or edema requiring medical treatment.

• Chronic disease requiring chronic or intermittent treatment with oral, intravenous, or injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible).

• Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months.

• Untreated hypo- or hyperthyroidism

• A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer.

• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgement of the Investigator, would preclude safe completion of the study.

• Blood pressure: SBP >170 or DBP > 100 mmHg

• Significant anemia (Hemoglobin < 11 g/dL for males and < 10 g/dL for females).

• Significant renal disease manifested by serum creatinine (> 1.5mg/dL for males or > 1.4mg/dL for females), or where the use of metformin is contra-indicated.

• Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 2.5 times upper limit of normal (ULN) or bilirubin >2x ULN).

• History of myopathy or history of elevated creatine kinase (CK) > 3 times upper normal limit.

• Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer).

• Women who are lactating, pregnant or planning to become pregnant during the course of the study.

• Unwillingness or inability to comply with the procedures described in this protocol.

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• Glipizide
oral anti-diabetic medication
• rosiglitazone maleate
oral antidiabetic medication

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Moron-Provincia de Buenos Aires
Argentina	GSK Investigational Site	Munro	Buenos Aires
Argentina	GSK Investigational Site	San Justo	Buenos Aires
Argentina	GSK Investigational Site	San Martín	Buenos Aires
Brazil	GSK Investigational Site	Ribeirão Preto	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Czech Republic	GSK Investigational Site	Hradec Kralove
France	GSK Investigational Site	Corbeil Essonnes Cedex
France	GSK Investigational Site	Le Plessis Robinson
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Rennes Cedex
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Coburg	Bayern
Germany	GSK Investigational Site	Dinslaken	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dormagen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duisburg	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Friedrichsthal	Saarland
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Herne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Herne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hirschhorn	Hessen
Germany	GSK Investigational Site	Kronach	Bayern
Germany	GSK Investigational Site	Kulmbach	Bayern
Germany	GSK Investigational Site	Lampertheim	Hessen
Germany	GSK Investigational Site	Leverkusen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Lichtenfels	Bayern
Germany	GSK Investigational Site	Ludwigshafen	Rheinland-Pfalz
Germany	GSK Investigational Site	Luenen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Marl	Nordrhein-Westfalen
Germany	GSK Investigational Site	Oberhausen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Saarlouis	Saarland
Germany	GSK Investigational Site	Speyer	Rheinland-Pfalz
Germany	GSK Investigational Site	Sr. Ingbert	Saarland
Germany	GSK Investigational Site	Trier	Rheinland-Pfalz
Germany	GSK Investigational Site	Trier	Rheinland-Pfalz
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Hong Kong	GSK Investigational Site	Causeway Bay
Hong Kong	GSK Investigational Site	Kowloon
Hong Kong	GSK Investigational Site	Kwun Tong
Hong Kong	GSK Investigational Site	Pokfulam
Hong Kong	GSK Investigational Site	Shatin
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	New Delhi
Italy	GSK Investigational Site	Rozzano (Mi)	Lombardia
Italy	GSK Investigational Site	Udine	Friuli-Venezia-Giulia
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon-Si
Latvia	GSK Investigational Site	Riga
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Nieuwegein
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Zwolle
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Kalisz
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Warszawa
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Spain	GSK Investigational Site	Alicante
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Marid
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	San Juan/Alicante
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Stockholm
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiang Mai
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Beaver	Pennsylvania
United States	GSK Investigational Site	Bellevue	Washington
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Burbank	California
United States	GSK Investigational Site	Camp Hill	Pennsylvania
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Corpus Christi	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Englewood	Colorado
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jackson	Tennessee
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Melbourne	Florida
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Mission Viejo	California
United States	GSK Investigational Site	New Brunswick	New Jersey
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Peoria	Illinois
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Springfield	Illinois
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	Springfield	Missouri
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Greece,  Hong Kong,  India,  Italy,  Korea, Republic of,  Latvia,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  Thailand, 

References & Publications (4)

García-García HM, Garg S, Brugaletta S, Morocutti G, Ratner RE, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Nesto RW, Serruys PW; APPROACH study group.. Evaluation of in-stent restenosis in the APPROACH trial (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History). Int J Cardiovasc Imaging. 2012 Mar;28(3):455-65. doi: 10.1007/s10554-011-9836-z. — View Citation

Gerstein HC, Ratner RE, Cannon CP, Serruys PW, García-García HM, van Es GA, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Fitzgerald PJ, Nesto RW; APPROACH Study Group.. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation. 2010 Mar 16;121(10):1176-87. doi: 10.1161/CIRCULATIONAHA.109.881003. — View Citation

Nesto RW. Effect of rosiglitazone versus glipizide on progression of coronary atherosclerosis in patients with type 2 diabetes and coronary artery disease. American Heart Association Scientific Sessions. November 12, 2008, New Orleans, LA. (http://directnews.americanheart.org/extras/pdfs/approach_slides.pdf)

Ratner RE, Cannon CP, Gerstein HC, Nesto RW, Serruys PW, Van Es GA, Kolatkar NS, Kravitz BG, Zalewski A, Fitzgerald PJ; APPROACH Study Group.. Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics. Am Heart J. 2008 Dec;156(6):1074-9. doi: 10.1016/j.ahj.2008.07.025. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Percent Atheroma Volume (PAV) to Month 18	The primary efficacy endpoint was change in PAV (defined as total atheroma volume divided by total vessel volume x 100) within a 40 mm segment in non-intervened coronary arteries from Baseline to Month 18, based upon Intravascular Ultrasound (IVUS) assessment.	Baseline to Month 18
Primary	Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18	Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD).	Baseline to Month 18
Secondary	Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Atheroma Volume to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Lumen Volume to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Vessel Volume to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Atheroma Area to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Lumen Area to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Vessel Area to Month 18	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Change From Baseline in Normalized Atheroma Volume	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort.	Baseline to Month 18
Secondary	Model Adjusted Change From Baseline in Normalized Atheroma Volume	IVUS-derived endpoints measured within the same segment (in non-intervened coronary arteries) from Baseline to Month 18. Normalized atheroma volume is defined as mean atheroma area x median segment length in cohort. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline	IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area	Baseline to Month 18
Secondary	Model Adjusted Change in Atheroma Volume Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline	IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline	IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area	Baseline to Month 18
Secondary	Model Adjusted Change in Atheroma Area Within the 10 mm of the Non-intervened Vessel Segment With the Greatest Atheroma Volume at Baseline	IVUS-derived endpoints measured within the same 10 mm segment of non-intervened coronary arteries with the greatest degree of atheroma volume at Baseline, from Baseline to Month 18, including the nominal change in atheroma volume and atheroma area. Model Adjusted Change = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior OAD Medication.	Baseline to Month 18
Secondary	Model Adjusted Change in Glycated Hemoglobin (HbA1c) From Baseline to Month 18	From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD) + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Model Adjusted Change in Fasting Plasma Glucose (FPG) From Baseline to Month 18	From repeated measures analysis model: Change = Baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Repeated Measures Analysis of Percent Change in hsCRP From Baseline to Month 18	Changes in cardiovascular biomarkers from Baseline to Month 18, such as high sensitivity C-reactive protein (hsCRP) . Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Repeated Measures Analysis of Percent Change in MMP 9 From Baseline to Month 18	Changes in cardiovascular biomarkers from Baseline to Month 18, such as matrix metalloproteinase-9 (MMP-9). Repeated measures analysis model: Log(value) - log(baseline) = log(baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18	It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1)It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Ratio to baseline as %change mean (%) was used as the estimation parameter for both groups.	Baseline to Month 18
Secondary	Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) From Baseline to Month 18	It was measured as ratio to baseline as percentage change based on log-transformed data : 100 x (exp(Mean change on log scale) - 1). Model Adjusted change based on ANCOVA: Log(value) - log(Baseline) = log(Baseline) + sex + region + treatment + prior OAD + cardiac procedure.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in Total Cholesterol (TC)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in High Density Lipoprotein Cholesterol (HDL-c)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in HDL-2	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in HDL-3	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in Low Density Lipoprotein Cholesterol (LDL-c)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in Triglycerides (TG)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in Free Fatty Acids (FFA)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Percent Change From Baseline to Month 18 in Apoprotein B (apoB)	Repeated measures analysis model: Log(value) - log (Baseline) = log(Baseline) + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Change From Baseline to Month 18 in LDL-c Peak Particle Density Measured by LDL Relative Flotation	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Change From Baseline to Month 18 in Total Cholesterol/HDL-c Ratio	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Change From Baseline to Month 18 in LDL-c/HDL-c Ratio	From repeated measures analysis model: Change = baseline + visit + sex + region + treatment + prior OAD + cardiac procedure + treatment x visit.	Baseline to Month 18
Secondary	Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for All-cause Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularization, or Hospitalization for Recurrent Myocardial Ischemia (MACE Composite 1)	This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.	Baseline to Month 21
Secondary	Number of Participants With the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for Cardiovascular Death, Nonfatal MI, or Nonfatal Stroke (MACE Composite 2)	This was 1 of 2 MACE composite endpoints and was a secondary efficacy endpoint.	Baseline to Month 21
Secondary	Number of Other Cardiovascular Events	This was one of the secondary endpoints of the study.	Baseline to Month 21

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.