BETonMACE: Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD

• Sponsor: Resverlogix Corp (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02586155
• Collaborator: PPD (Industry), ICON plc (Industry), Medidata Solutions (Industry)
• Enrollment: 2,425
• Locations: 214
• Arms: 2
• Actual Duration (Months): 67.6
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether bromodomain extraterminal domain (BET) inhibition treatment with RVX000222 in high-risk type 2 diabetes mellitus patients with coronary artery disease increases the time to major adverse cardiovascular events.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2; Coronary Artery Disease	Drug: Apabetalone; Drug: Placebo; Drug: Atorvastatin; Drug: Rosuvastatin	Phase 3

Detailed Description

The majority (75%) of deaths in subjects with diabetes mellitus (DM) are due to atherosclerotic cardiovascular disease (CVD). Recent studies suggest a major adverse cardiovascular event (MACE) rate of >11% over 18 months in type 2 diabetes mellitus (T2DM) despite a baseline LDL-C of <2.1 mmol/L. Bromodomains (BRDs) are a family of evolutionary conserved protein-interaction modules that play key functions in chromatin organization and regulation of gene transcription. One recognized family of bromodomain-containing proteins is the bromodomain and extra-terminal (BET) family. BET inhibition represents a novel, epigenetic approach to treat CAD.

RVX000222 affects biological processes important in atherosclerosis and acute coronary events via selective inhibition of BET proteins. RVX000222 is available as a capsule formulation with standard excipients and established stability.

The BETonMACE study will focus on prevention of subsequent MACE in subjects with CAD and DM with high intensity statin therapy as co-medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2425 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase III Multi-Center, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Clinical Trial in High-Risk Type 2 Diabetes Mellitus (T2DM) Subjects With Coronary Artery Disease (CAD) to Determine Whether Bromodomain Extraterminal Domain (BET) Inhibition Treatment With RVX000222 Increases the Time to Major Adverse Cardiovascular Events (MACE)
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Nov 30, 2020
• Actual Study Completion Date: Jun 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High-Intensity statin therapy+RVX000222 Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)	Drug: Apabetalone; 100 mg capsule; Other Names: RVX000222 ; Drug: Atorvastatin; High-Intensity Statin; Other Names: Lipitor ; Drug: Rosuvastatin; High-Intensity Statin; Other Names: Crestor
Active Comparator: High-Intensity statin therapy+Placebo Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)	Drug: Placebo; Capsule manufactured to mimic RVX000222 100 mg capsule; Other Names: Placebo (for RVX000222) ; Drug: Atorvastatin; High-Intensity Statin; Other Names: Lipitor ; Drug: Rosuvastatin; High-Intensity Statin; Other Names: Crestor

Outcome Measures

Primary Outcome Measures

1. Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE [120 weeks]

   Incidence of first occurrence of MACE narrowly defined as a single composite endpoint of Cardiovascular (CV) Death (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI) or Stroke. If a subject has multiple events, only the first event contributing to the composite endpoint is counted.

Secondary Outcome Measures

1. Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE [120 weeks]

   First occurrence of MACE broadly defined as a single composite endpoint of Cardiovascular Death (CVD) (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI), Stroke, or Hospitalization for CVD events (including unstable angina and evidence of new or presumed new progressive obstructive coronary disease or emergency revascularization procedures at any time and urgent revascularization procedures ≥30 days after the index event as defined by Hicks et al., 2014) . If a subject has multiple events, only the first event contributing to the composite endpoint is counted.

2. Incidence of Hospitalization for Congestive Heart Failure (CHF) [120 weeks]

3. Incidence of All-cause Mortality [120 weeks]

4. Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups [120 weeks]

5. Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups [120 weeks]

6. Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups [120 weeks]

7. Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups [120 weeks]

8. Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups [120 weeks]

9. Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups [120 weeks]

10. Change in Glucose From Baseline Over Time Between and Within Treatment Groups [120 weeks]

11. Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups [172 weeks]

12. Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups [52 weeks]

13. Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time Within and Between Treatment Groups for Subjects With Impaired Renal Function at Baseline (eGFR <60 mL/Min/1.7m2) [120 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ACS event of either unstable angina or myocardial infarction 7-90 days prior Visit 1:

Unstable angina: for a qualifying unstable angina event, each of components (a), (b), and (c) must be satisfied: a.) Characteristic ischemic pain or discomfort in chest/associated referral areas, occurring at rest/with minimal exertion b.) ECG changes consistent with acute myocardial ischemia based on new/presumed ST elevation/depression or T-wave inversion c.) Objective evidence of obstructive CAD based on 1+ of the following: i. New/presumed new evidence of myocardial ischemia/infarction by perfusion imaging ii. New/presumed new regional wall motion abnormality iii. Current evidence of at least 1 epicardial coronary artery stenosis ≥70% by coronary angiography iv. Need for coronary revascularization for the index ACS event, including a percutaneous coronary intervention (PCI) with or without coronary stenting.

Prior MI 7-90 days prior screening treated with or without a percutaneous coronary intervention (PCI). For a qualifying event of MI 2 of the following 3 criteria must be satisfied: a.) Characteristic ischemic chest pain/pain in associated referral areas b.) Dynamic elevation of troponin T/I or CKMB if troponinT/I is unavailable at local lab (at least >ULN for lab) c.) Development of new Q-waves in ≥2 adjacent ECG leads or development of new dominant R wave in V1

• Documented diagnosis of T2DM (1+ of the following criteria): Documented history of T2DM, History of taking diabetes medication, and/or HbA1c ≥6.5% at Visit 1

• For males HDL-C<40 mg/dL(1.04 mmol/L), for females HDL-C<45 mg/dL(1.17 mmol/L) at Visit 1

• Subjects currently not on high intensity statin therapy could start rosuvastatin at Visit 1 and those currently on therapy besides atorvastatin/rosuvastatin can be switched to rosuvastatin at Visit 1

• Female subjects of non-childbearing potential (post-surgical sterilization/post-menopausal) or if childbearing potential have neg urine pregnancy test and be willing and able to use non-hormonal birth control (non-hormonal IUD, condom or diaphragm) or remain abstinent from Screening to Follow-up Visit

• Give signed informed consent

Exclusion Criteria:

• Heart disease which will w/in 90 days of Visit 1 likely need coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement

• Previous/current diagnosis of severe heart failure or documented LVEF<25% determined by contrast left ventriculography, radionuclide ventriculography or echocardiography. Absence of LVEF measurement in subject w/out a previous/current diagnosis of heart failure does not exclude entry into study

• Evidence of cardiac EP instability incl. history of uncontrolled ventricular arrhythmias, atrial fibrillation/flutter or supraventricular tachycardias w/ a ventricular response HR>100bpm at rest w/in 4 wks prior Visit 1

• CABG w/in 90 days prior Visit 1

• Evidence of severe renal impairment as determined by either eGFR<30 mL/min/1.7m2 at Visit 1 or current need for dialysis

• Uncontrolled hypertension defined as 2 consecutive measurements of sitting BP of systolic>180 mmHg or diastolic>100 mmHg at Visit 1

• Treatment w/ immunosuppressants w/in 12 mos prior Visit 1

• Use of fibrates at any dose or niacin/nicotinic acid 250+ mg w/in 30 days prior Visit 1

• Known allergy/sensitivity to any ingredient in IMP

• History of intolerance to atorvastatin/rosuvastatin

• Triglycerides>400 mg/dL (4.52 mmol/L) at Visit 1

• Any medical/surgical condition which might significantly alter absorption, distribution, metabolism or excretion of medication

• Evidence of cirrhosis from liver imaging/biopsy, history of hepatic encephalopathy, esophageal/gastric varices, active hepatitis or prior porta-caval shunt procedure or a Child-Pugh score of ≥5 points

• ALT/AST>1.5xULN by central lab at Visit 1

• Tot. bilirubin>ULN by central lab at Visit 1

• History of malignancy of any organ syst treated/untreated w/in the past 2 yrs whether or not there is evidence of local recurrence/metastases except localized basal skin cell carcinoma

• History/evidence of drug/alcohol abuse w/in 12 mos of Visit 1

• Pregnancy

• Any condition which may place subject at higher risk from his/her participation in the study or is likely to prevent subject from completing/complying w/ requirements of study

• Use of other investigational drugs and devices w/in 30 days or 5 half-lives of Visit 1, whichever is longer

• History of noncompliance to medical regimens or unwillingness to comply w/ study protocol

• Any condition that would confound the evaluation/interpretation of efficacy and/or safety data

• Persons directly involved in execution of this protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Investigaciones Clinicas Bahia Blanca	Bahía Blanca		Argentina
2	Bioclinica Buenos Aires	Buenos Aires		Argentina
3	Centro Privado de Enfermedades Cardiovasculares	Buenos Aires		Argentina
4	Consultorios Asociados Endocronología E Investigación Clínica Aplicada	Buenos Aires		Argentina
5	Instituto Cardiovascular de Buenos Aires	Buenos Aires		Argentina
6	Sanatorio Guemes	Buenos Aires		Argentina
7	Clinica Coronel Suarez	Coronel Suárez		Argentina
8	Instituto de Cardiologia de Corrientes Juana Francisca Cabral	Corrientes		Argentina
9	CEMAIC	Córdoba		Argentina
10	Centro Médico Colón	Córdoba		Argentina
11	Centro Médico Luquez	Córdoba		Argentina
12	Clínica Privada Del Prado Sociedad de Responsabilidad Limitada	Córdoba		Argentina
13	Fundación Clínica Colombo	Córdoba		Argentina
14	Hospital Cordoba	Córdoba		Argentina
15	Hospital San Roque	Córdoba		Argentina
16	Instituto Del Corazón	Córdoba		Argentina
17	Instituto Modelo de Cardiologia	Córdoba		Argentina
18	Instituto Médico DAMIC	Córdoba		Argentina
19	Ipac Caraffa	Córdoba		Argentina
20	Sanatorio Allende	Córdoba		Argentina
21	Centro Médico Libertad	Haedo		Argentina
22	CIMEL	Lanús		Argentina
23	Instituto de Investigaciones Clínicas Mar Del Plata	Mar Del Plata		Argentina
24	Hospital Central	Mendoza		Argentina
25	DIM Clinica Privada	Ramos Mejia		Argentina
26	Instituto de Hematologia Y Medicina Clinica	Rosario		Argentina
27	Sanatorio Britanico de Rosario	Rosario		Argentina
28	Prevencion Cardio Vascular	Salta		Argentina
29	Grupo Medico Alem	San Isidro		Argentina
30	Bioclinica Tucumán	San Miguel De Tucumán		Argentina
31	Centro Modelo de Cardiologia	San Miguel De Tucumán		Argentina
32	Investigaciones Clinicas Tucuman	San Miguel De Tucumán		Argentina
33	Centro de Investigaciones Clínicas Del Litoral SRL	Santa Fe		Argentina
34	Sanatorio San Francisco	Santiago Del Estero		Argentina
35	Clínica FUSAVIM Privada	Villa María		Argentina
36	Instituto de Investigaciones Clínicas Zárate	Zárate		Argentina
37	Flinders Medical Centre	Bedford Park		Australia
38	ZNA Middelheim	Antwerpen		Belgium
39	Imelda VZW	Bonheiden		Belgium
40	AZ Turnhout	Turnhout		Belgium
41	Multiprofile Hospital For Active Treatment Dr Tota Venkova	Gabrovo		Bulgaria
42	Multiprofile Hospital for Active Treatment - Prof. Dr. Paraskev Stoyanov AD	Lovech		Bulgaria
43	Multiprofile Hospital For Active Treatment - Pazardzhik AD	Pazardzhik		Bulgaria
44	University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD	Pleven		Bulgaria
45	Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD	Smolyan		Bulgaria
46	Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda	Sofia		Bulgaria
47	City Clinic University Multiprofile Hospital for Active Treatment EOOD	Sofia		Bulgaria
48	Medical Center Kardiohelp EOOD	Sofia		Bulgaria
49	Second Multiprofile Hospital for Active Treatment Sofia	Sofia		Bulgaria
50	Synexus Affiliate - Diagnostic and Consulting Center Ascendent	Sofia		Bulgaria
51	University Multiprofile Hospital for Active Treatment Aleksandrovska EAD	Sofia		Bulgaria
52	University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD	Sofia		Bulgaria
53	Medical Center Orfey OOD	Stara Zagora		Bulgaria
54	Multiprofile Hospital for Active Treatment Sveta Marina EAD	Varna		Bulgaria
55	General Hospital Karlovac	Karlovac		Croatia
56	Special Hospital for medicinal rehabilitation Krapinske Toplice	Krapinske Toplice		Croatia
57	Clinical Hospital Osijek	Osijek		Croatia
58	General Hospital Dr Josip Bencevic	Slavonski Brod		Croatia
59	General Hospital Virovitica	Virovitica		Croatia
60	Clinical Hospital Sveti duh	Zagreb		Croatia
61	DRK Kliniken Berlin Westend	Berlin		Germany
62	Medizinisches Versorgungszentrum am Küchwald GmbH	Chemnitz		Germany
63	Zentrum für Klinische Prüfung in der Facharztzentrum Dresden Neustadt Gbr	Dresden		Germany
64	Katholisches Krankenhaus St. Johann Nepomuk	Erfurt		Germany
65	Heidelberger Praxisklinik für Kardiologie	Heidelberg		Germany
66	Klinikum Hoyerswerda	Hoyerswerda		Germany
67	Studienzentrum Dr.Appel	Kassel		Germany
68	Asklepios Klinik Langen	Langen		Germany
69	Klinikum Leverkusen GmbH	Leverkusen		Germany
70	Bajai Szent Rókus Kórház	Baja		Hungary
71	Grof Tisza Istvan Korhaz Berettyoujfalu	Berettyóújfalu		Hungary
72	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest		Hungary
73	Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet	Budapest		Hungary
74	Gottsegen Gyorgy Orszagos Kardiologiai Intezet	Budapest		Hungary
75	Magyar Honvédség Egészségügyi Központ	Budapest		Hungary
76	Semmelweis Egyetem	Budapest		Hungary
77	Synexus (DRS) - Synexus Magyarország Kft. Budapest	Budapest		Hungary
78	Szent Margit Korhaz	Budapest		Hungary
79	Szent Rókus Kórház és Intézményei	Budapest		Hungary
80	Selye János Kórház	Komárom		Hungary
81	TaNaMed Kft.	Mosonmagyaróvár		Hungary
82	Kanizsai Dorottya Kórház	Nagykanizsa		Hungary
83	Coromed-SMO Kft.	Pécs		Hungary
84	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary
85	Tolna Megyei Balassa János Kórház	Szekszárd		Hungary
86	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár		Hungary
87	Barzilai Medical Center	Ashkelon		Israel
88	Soroka University Medical Centre	Be'er Sheva		Israel
89	Hillel Yaffe Medical Center	Hadera		Israel
90	Bnei Zion Medical Center	Haifa		Israel
91	Lady Davis Carmel Medical Center	Haifa		Israel
92	Linn Medical Center Clalit Health Services	Haifa		Israel
93	Rambam Medical Center	Haifa		Israel
94	Edith Wolfson Medical Center	Holon		Israel
95	Hadassah University Hospital Ein Kerem	Jerusalem		Israel
96	Hadassah University Hospital Mount Scopus	Jerusalem		Israel
97	Shaare Zedek Medical Center	Jerusalem		Israel
98	Meir Medical Center	Kefar-Sava		Israel
99	Galilee Medical Center	Nahariya		Israel
100	Nazareth EMMS Hospital	Nazareth		Israel
101	Chaim Sheba Medical Center	Ramat Gan		Israel
102	Kaplan Medical Center	Rehovot		Israel
103	ZIV Medical Center	Safed		Israel
104	Clalit Health Medical Center	Tel Aviv		Israel
105	Tel Aviv Sourasky Medical Center	Tel-Aviv		Israel
106	Baruch Padeh Poriya Medical Center	Tiberias		Israel
107	Fundacion Cardiovascular de Aguascalientes AC	Aguascalientes		Mexico
108	Hospital Cardiológica Aguascalientes	Aguascalientes		Mexico
109	Investigacion en Salud y Metabolismo S.C.	Chihuahua		Mexico
110	Centro de Investigación Biomedica y Farmaceutica	Ciudad de México		Mexico
111	Clinica Integral del Paciente Diabetico y Obeso	Ciudad De México		Mexico
112	Fundación de Atención e Investigación Médica Lindavista S.C.	Ciudad de México		Mexico
113	Centro Para el Desarrollo de la Medicina y de Asistencia Especializada SC	Culiacan		Mexico
114	Centro de Investigacion y Atencion de Diabetes, Endocrinologia y Nutricion	Durango		Mexico
115	Arechavaleta Granell Maria del Rosario	Guadalajara		Mexico
116	Centro de Investigacion Medica Biologica Y de Terapia Avanzada SC	Guadalajara		Mexico
117	Unidad de Investigacion Clinica Cardiometabolica de Occidente SC	Guadalajara		Mexico
118	Hospital Angeles Leon	León De Los Aldama		Mexico
119	Centro de Desarrollo Biomédico	Merida		Mexico
120	Sanatorio y Servicios Médicos Obregón S.A. de C.V.	Mexico City		Mexico
121	Instituto Cardiovascular de Monclova	Monclova		Mexico
122	Hospital Universitario Dr. Jose Eleuterio González	Monterrey		Mexico
123	IMED Internal Medicine Clin Trials	Monterrey		Mexico
124	Unidad de Investigación Clínica En Medicina SC	Monterrey		Mexico
125	Diabetes Total, S.A de C.V.	Pachuca		Mexico
126	Investigacion Biomedica Aplicada de Hidalgo S.A. de C.V.	Pachuca		Mexico
127	Cardioarritmias e Investigación S.C.	San Luis Potosi		Mexico
128	Hospital Central Dr Ignacio Morones Prieto	San Luis Potosí		Mexico
129	INBIOMEDYC Toluca	Toluca		Mexico
130	Centro de Alta Especialidad Dr. Rafael Lucio	Veracruz		Mexico
131	Dr. Humberto Alvarez Lopez	Zapopan		Mexico
132	Meander Medisch Centrum	Amersfoort		Netherlands
133	OLVG locatie Oost	Amsterdam		Netherlands
134	VU Medisch Centrum	Amsterdam		Netherlands
135	Podlaski Osrodek Kardiologii Poradnia Prywatna	Bialystok		Poland
136	Malopolskie Centrum Sercowo-Naczyniowe	Chrzanow		Poland
137	Polsko-Amerykanskie Kliniki Serca	Dabrowa Gornicza		Poland
138	Gabinet Kardiologiczno-Internistyczny	Gdynia		Poland
139	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych Promont-Med.	Kielce		Poland
140	Diamond Clinic	Kraków		Poland
141	Szpital Specjalistyczny im. Jozefa Dietla w Krakowie	Kraków		Poland
142	Zespol Przychodni Specjalistycznych DIAB-END-COR Sp. z o.o.	Kraków		Poland
143	Prywatna Praktyka Lekarska MAZ-MEDICA Maciej R.Mazurkiewicz	Lodz		Poland
144	Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow	Lódz		Poland
145	Polsko-Amerykanskie Kliniki Serca	Nysa		Poland
146	Pro Corde, Dom Medyczny	Opole		Poland
147	Medicome Sp. z o.o.	Oswiecim		Poland
148	Rodzinne Centrum Zdrowia	Otwock		Poland
149	Niepubliczny Zaklad Opieki Zdrowotnej Specjalistyczna Przychodnia Lekarska "MEDIKARD"	Plock		Poland
150	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne SBB	Tarnobrzeg		Poland
151	Centrum Medyczne doktorA	Warszawa		Poland
152	Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego	Warszawa		Poland
153	Niepubliczny Zaklad Opieki Zdrowotnej AURUM	Warszawa		Poland
154	Centrum Kardiologiczne Pro Corde Sp. z o.o. Niepubliczny Zaklad Opieki Zdrowotnej	Wroclaw		Poland
155	Wro Medica	Wroclaw		Poland
156	City Clinical Hospital #6	Chelyabinsk		Russian Federation
157	Ural State Medical University	Ekaterinburg		Russian Federation
158	Federal Budget Healthcare Institution Medici - sanitary unit of Ministry of internal affairs of Russ	Kemerovo		Russian Federation
159	Research Institute of Complex Cardiovascular Pathology	Kemerovo		Russian Federation
160	Krasnodar Regional Clinical Hospital #2	Krasnodar		Russian Federation
161	Moscow City State Budgetary Healthcare Institution City Clinical Hospital named after V.V. Veresayev	Moscow		Russian Federation
162	Russian Cardiology Research and Production Center	Moscow		Russian Federation
163	City Hospital 13	Nizhniy Novgorod		Russian Federation
164	State Budgetary Healthcare Institution of Novosibirsk Region City Clinical Hospital No. 19	Novosibirsk		Russian Federation
165	Republican Hospital n.a. V.A. Baranov	Petrozavodsk		Russian Federation
166	Municipal Budgetary Healthcare Institution City Emergency Hospital	Rostov-on-Don		Russian Federation
167	International Medical Center SOGAZ	Saint Petersburg		Russian Federation
168	North-West State Medical University n.a. I.I. Mechnikov	Saint Petersburg		Russian Federation
169	St Petersburg City Outpatient Clinic #109	Saint Petersburg		Russian Federation
170	Saratov State Medical University	Saratov		Russian Federation
171	State Healthcare Institution Regional Clinical Cardiologic Dispensary	Saratov		Russian Federation
172	City Hospital #4	Sochi		Russian Federation
173	Research Cardiology Institute of Tomsk Scientific Center of RAMS Siberian Branch	Tomsk		Russian Federation
174	State Budgetary Healthcare Institution of Vladimir Region City Hospital No. 4	Vladimir		Russian Federation
175	Clinical Center of Serbia	Belgrade		Serbia
176	Clinical Hospital Centar Zvezdara	Belgrade		Serbia
177	Clinical Hospital Center Bezanijska Kosa	Belgrade		Serbia
178	Clinical Hospital Centre Zemun	Belgrade		Serbia
179	Euromedik	Belgrade		Serbia
180	Institute of Cardiovascular Diseases Dedinje	Belgrade		Serbia
181	KBC Dr Dragisa Misovic Dedinje	Belgrade		Serbia
182	Military Medical Academy	Belgrade		Serbia
183	Clinical Center Kragujevac	Kragujevac		Serbia
184	Institute Niska Banja	Niska Banja		Serbia
185	Clinical Center Nis	Nis		Serbia
186	Clinical Centre of Vojvodina	Novi Sad		Serbia
187	Institute of Cardiovascular Diseases of Vojvodina	Sremska Kamenica		Serbia
188	General Hospital Uzice	Uzice		Serbia
189	Health Center Zajecar	Zajecar		Serbia
190	ALIAN, s.r.o	Bardejov		Slovakia
191	CARDIOCONSULT, s.r.o.	Bratislava		Slovakia
192	Univerzitna nemocnica Bratislava	Bratislava		Slovakia
193	Kardio-Onkologia, s.r.o.	Dolny Kubin		Slovakia
194	CARDIO D&R, s.r.o. Kosice	Kosice		Slovakia
195	Zeleznicne zdravotnictvo Kosice, s.r.o.	Kosice		Slovakia
196	KARDIOMED s.r.o.	Lucenec		Slovakia
197	MEDI M&M s.r.o.	Moldava nad Bodvou		Slovakia
198	Nemocnica s poliklinikou Nove Mesto nad Vahom n.o.	Nove Mesto nad Vahom		Slovakia
199	Cardioinvest s. r. o.	Nove Zamky		Slovakia
200	DIAB s.r.o.	Roznava		Slovakia
201	MEDIVASA, s.r.o.	Zilina		Slovakia
202	Changhua Christian Hospital	Changhua		Taiwan
203	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
204	Kaohsiung Veterans General Hospital	Kaohsiung		Taiwan
205	Mackay Memorial Hospital-Taipei branch	New Taipei City		Taiwan
206	China Medical University Hospital	Taichung		Taiwan
207	National Cheng Kung University Hospital	Tainan City		Taiwan
208	Tri-Service General Hospital	Taipei City		Taiwan
209	Cathay General Hospital	Taipei		Taiwan
210	Chi Mei Medical Center	Taipei		Taiwan
211	Far Eastern Memorial Hospital	Taipei		Taiwan
212	National Taiwan University Hospital	Taipei		Taiwan
213	Taipei Veterans General Hospital	Taipei		Taiwan
214	Chang Gung Medical Foundation Linkou Branch (Clinical Research Center)	Taoyuan City		Taiwan

Sponsors and Collaborators

• Resverlogix Corp
• PPD
• ICON plc
• Medidata Solutions

Investigators

• Study Chair: Kausik Ray, MD, Imperial College London

Study Documents (Full-Text)

• Study Protocol - Oct 31, 2017
• Statistical Analysis Plan - Jun 10, 2019

More Information

Additional Information:

• Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes A Randomized Clinical Trial

Publications

None provided.

• Responsible Party: Resverlogix Corp
• ClinicalTrials.gov Identifier: NCT02586155
• Other Study ID Numbers: RVX222-CS-015
• First Posted: Oct 26, 2015
• Last Update Posted: Aug 20, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Atorvastatin; Rosuvastatin Calcium

Study Results

Participant Flow

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Period Title: Overall Study
STARTED	1215	1210
Final Number Randomized	1212	1206
COMPLETED	1088	1083
NOT COMPLETED	127	127

Baseline Characteristics

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo	Total
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Total of all reporting groups
Overall Participants	1212	1206	2418
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.0	62.0	62.0
Age, Customized (Count of Participants)
≤65 years	816 67.3%	772 64%	1588 65.7%
>65 years	396 32.7%	434 36%	830 34.3%
Sex: Female, Male (Count of Participants)
Female	305 25.2%	313 26%	618 25.6%
Male	907 74.8%	893 74%	1800 74.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	27 2.2%	31 2.6%	58 2.4%
Asian	20 1.7%	19 1.6%	39 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1063 87.7%	1056 87.6%	2119 87.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	102 8.4%	100 8.3%	202 8.4%
Body weight (kilograms (kg)) [Median (Full Range) ]
Median (Full Range) [kilograms (kg)]	85.75	85.90	85.90
Body-mass index (BMI) (kg/m2) [Median (Full Range) ]
Median (Full Range) [kg/m2]	29.589	29.585	29.585

Outcome Measures

1. Primary Outcome

Title	Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE
Description	Incidence of first occurrence of MACE narrowly defined as a single composite endpoint of Cardiovascular (CV) Death (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI) or Stroke. If a subject has multiple events, only the first event contributing to the composite endpoint is counted.
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
CV Death	34	42
Non-fatal MI	76	92
Stroke	15	15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Intensity Statin Therapy+RVX000222, High-Intensity Statin Therapy+Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1070
	Comments
	Method	Stratified long-rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.823
	Confidence Interval	(2-Sided) 95%; 0.649 to 1.044
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE
Description	First occurrence of MACE broadly defined as a single composite endpoint of Cardiovascular Death (CVD) (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI), Stroke, or Hospitalization for CVD events (including unstable angina and evidence of new or presumed new progressive obstructive coronary disease or emergency revascularization procedures at any time and urgent revascularization procedures ≥30 days after the index event as defined by Hicks et al., 2014) . If a subject has multiple events, only the first event contributing to the composite endpoint is counted.
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
CV Death	33	42
Non-fatal MI	74	91
Hospitalization for CVD events	22	18
Stroke	15	15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Intensity Statin Therapy+RVX000222, High-Intensity Statin Therapy+Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1495
	Comments
	Method	Stratified long-rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.849
	Confidence Interval	(2-Sided) 95%; 0.679 to 1.061
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Incidence of Hospitalization for Congestive Heart Failure (CHF)
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
Number [events]	29	48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Intensity Statin Therapy+RVX000222, High-Intensity Statin Therapy+Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Stratified long-rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Incidence of All-cause Mortality
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1207
Count of Participants [Participants]	61 5%	72 6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Intensity Statin Therapy+RVX000222, High-Intensity Statin Therapy+Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Stratified long-rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

A select subset of subjects were analyzed for ApoA-I, Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	243	238
Baseline	119.0	117.5
Visit 11 (Week 24)	128.0	125.0
Visit 14 (Week 52)	129.0	124.0
Visit 16 (Week 76)	132.0	125.0
Visit 18 (Week 100)	131.0	125.0
Last Visit on Treatment (LVT)	132.5	129.0
Follow-up	131.0	127.0

6. Secondary Outcome

Title	Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

A select subset of subjects were analyzed for ApoB, Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	243	238
Baseline	66.0	66.0
Visit 11 (Week 24)	68.5	68.0
Visit 14 (Week 52)	70.0	68.0
Visit 16 (Week 76)	70.5	69.0
Visit 18 (Week 100)	70.5	72.0
Last Visit on Treatment (LVT)	68.0	72.0
Follow-up	70.0	71.0

7. Secondary Outcome

Title	Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

All subjects were analyzed and contributed LDL-C data for the 'High-Intensity Statin Therapy + RVX000222' and the 'High-Intensity statin therapy + Placebo' arms. Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
Baseline	1.690	1.690
Visit 11 (Week 24)	1.530	1.530
Visit 14 (Week 52)	1.590	1.655
Visit 16 Week 76)	1.600	1.660
Visit 18 Week 100)	1.660	1.725
Last Visit on Treatment (LVT)	1.700	1.745
Follow-up	1.650	1.680

8. Secondary Outcome

Title	Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

All subjects were analyzed and contributed HDL-C data for the 'High-Intensity Statin Therapy + RVX000222' and the 'High-Intensity statin therapy + Placebo' arms. Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
Baseline	0.870	0.860
Visit 11 (Week 24)	0.970	0.940
Visit 14 (Week 52)	0.970	0.930
Visit 16 Week 76)	0.960	0.920
Visit 18 Week 100)	0.970	0.910
Last Visit on Treatment (LVT)	0.990	0.960
Follow-up	1.010	0.950

9. Secondary Outcome

Title	Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

All subjects were analyzed and contributed TG data for the 'High-Intensity Statin Therapy + RVX000222' and the 'High-Intensity statin therapy + Placebo' arms. Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
Baseline	1.630	1.690
Visit 11 (Week 24)	1.660	1.670
Visit 14 (Week 52)	1.735	1.700
Visit 16 Week 76)	1.730	1.670
Visit 18 Week 100)	1.755	1.610
Last Visit on Treatment (LVT)	1.700	1.650
Follow-up	1.650	1.720

10. Secondary Outcome

Title	Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

All subjects were analyzed and contributed HbA1c data for the 'High-Intensity Statin Therapy + RVX000222' and the 'High-Intensity statin therapy + Placebo' arms Subject data is missing across time points

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1207
Baseline	7.40	7.30
Visit 11 (Week 24)	7.20	7.20
Visit 14 (Week 52)	7.30	7.30
Visit 16 (Week 76)	7.30	7.40
Visit 18 (Week 100)	7.30	7.30
LVT	7.40	7.30
Follow-up	7.30	7.20

11. Secondary Outcome

Title	Change in Glucose From Baseline Over Time Between and Within Treatment Groups
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

All subjects were analyzed and contributed glucose data for the 'High-Intensity Statin Therapy + RVX000222' and the 'High-Intensity statin therapy + Placebo' arms. Subject data is missing across time points

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1207
Baseline	7.590	7.385
Visit 11 (Week 24)	7.925	7.835
Visit 14 (Week 52)	7.900	7.800
Visit 16 (Week 76)	7.920	7.840
Visit 18 (Week 100)	8.010	7.890
LVT	8.100	7.795
Follow-up	7.650	7.595

12. Secondary Outcome

Title	Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups
Time Frame	172 weeks

Outcome Measure Data

Analysis Population Description

Subject data is missing across time points

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1207
Baseline	78.0	77.0
Visit 3 (Week 2)	71.0	76.0
Visit 4 (Week 4)	70.0	75.0
Visit 5 (Week 6)	70.0	75.0
Visit 6 (Week 8)	69.0	76.0
Visit 7 (Week 10)	69.0	75.0
Visit 8 (Week 12)	69.0	75.0
Visit 9 (Week 16)	68.0	75.0
Visit 10 (Week 20)	68.0	74.0
Visit 11 (Week 24)	68.0	75.0
Visit 12 (Week 28)	69.0	74.0
Visit 13 (Week 40)	69.0	74.0
Visit 14 (Week 52)	71.0	76.0
Visit 15 (Week 64)	71.0	74.5
Visit 16 (Week 76)	70.0	76.0
Visit 17 (Week 88)	72.0	76.0
Visit 18 (Week 100)	72.0	75.0
Visit 19 (Week 112)	71.0	75.0
Visit 20 (Week 124)	71.0	77.0
Visit 21 (Week 136)	69.5	77.0
Visit 22 (Week 148)	69.0	76.0
Visit 23 (Week 160)	68.0	78.0
Visit 24 (Week 172)	75.5	83.0
Last Visit on Treatment (LVT)	72.0	77.0
Follow-up	76.0	76.0

13. Secondary Outcome

Title	Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

A select subset of subjects in two countries were analyzed for CRP, Subject data is missing across time points.

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	244	239
Baseline	2.875	2.740
Visit 8 (Week 12)	1.755	1.805
Visit 14 (Week 52)	1.710	1.580

14. Secondary Outcome

Title	Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time Within and Between Treatment Groups for Subjects With Impaired Renal Function at Baseline (eGFR <60 mL/Min/1.7m2)
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

Subject data is missing across time points

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	121	162
Baseline	51.4	48.9
Visit 11 (Week 24)	53.0	53.3
Visit 14 (Week 52)	52.4	52.5
Visit 16 (Week 76)	50.8	54.8
Visit 18 (Week 100)	46.5	56.7
LVT	52.5	53.9

15. Post-Hoc Outcome

Title	Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE
Description	First occurrence of four-point MACE defined as a single composite endpoint of cardiovascular (CV) death (including undetermined cause of death) or non-fatal myocardial infarction (MI), stroke or hospital admission for congestive heart failure.
Time Frame	120 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Intensity Statin Therapy+RVX000222	High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin	Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
Measure Participants	1212	1206
CV Death (CVD)	45	55
Non-fatal MI	77	94
Stroke	17	17
First Hospitalization for CHF	29	48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Intensity Statin Therapy+RVX000222, High-Intensity Statin Therapy+Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.63 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	120 weeks
Arm/Group Title	High-Intensity Statin Therapy+RVX000222		High-Intensity Statin Therapy+Placebo
Arm/Group Description	Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Apabetalone: 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin		Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin) Placebo: Capsule manufactured to mimic RVX000222 100 mg capsule Atorvastatin: High-Intensity Statin Rosuvastatin: High-Intensity Statin
All Cause Mortality
	High-Intensity Statin Therapy+RVX000222		High-Intensity Statin Therapy+Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/1212 (5%)		72/1207 (6%)
Serious Adverse Events
	High-Intensity Statin Therapy+RVX000222		High-Intensity Statin Therapy+Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	354/1212 (29.2%)		339/1207 (28.1%)
Blood and lymphatic system disorders
Anaemia	4/1212 (0.3%)		1/1207 (0.1%)
Hypochromic anaemia	2/1212 (0.2%)		0/1207 (0%)
Iron deficiency anaemia	0/1212 (0%)		1/1207 (0.1%)
Cardiac disorders
Angina unstable	57/1212 (4.7%)		39/1207 (3.2%)
Acute myocardial infarction	42/1212 (3.5%)		49/1207 (4.1%)
Angina pectoris	32/1212 (2.6%)		32/1207 (2.7%)
Cardiac failure	11/1212 (0.9%)		28/1207 (2.3%)
Myocardial infarction	14/1212 (1.2%)		11/1207 (0.9%)
Atrial fibrillation	10/1212 (0.8%)		10/1207 (0.8%)
Cardiac failure congestive	6/1212 (0.5%)		9/1207 (0.7%)
Coronary artery disease	9/1212 (0.7%)		6/1207 (0.5%)
Acute coronary syndrome	5/1212 (0.4%)		9/1207 (0.7%)
Cardiac failure acute	8/1212 (0.7%)		6/1207 (0.5%)
Coronary artery stenosis	5/1212 (0.4%)		4/1207 (0.3%)
Myocardial ischemia	5/1212 (0.4%)		3/1207 (0.2%)
Cardiac failure chronic	2/1212 (0.2%)		5/1207 (0.4%)
Cardiac arrest	1/1212 (0.1%)		5/1207 (0.4%)
Cardiogenic shock	2/1212 (0.2%)		4/1207 (0.3%)
Atrial flutter	3/1212 (0.2%)		1/1207 (0.1%)
Ischaemic cardiomyopathy	2/1212 (0.2%)		2/1207 (0.2%)
Ventricular tachycardia	3/1212 (0.2%)		1/1207 (0.1%)
Atrioventricular block complete	0/1212 (0%)		3/1207 (0.2%)
Supraventricular tachycardia	0/1212 (0%)		3/1207 (0.2%)
Ventricular fibrillation	1/1212 (0.1%)		2/1207 (0.2%)
Coronary artery occlusion	0/1212 (0%)		2/1207 (0.2%)
Left ventricular failure	2/1212 (0.2%)		0/1207 (0%)
Mitral valve incompetence	2/1212 (0.2%)		0/1207 (0%)
Anginal equivalent	0/1212 (0%)		1/1207 (0.1%)
Aortic valve incompetence	1/1212 (0.1%)		0/1207 (0%)
Aortic valve stenosis	0/1212 (0%)		1/1207 (0.1%)
Arrhythmia	0/1212 (0%)		1/1207 (0.1%)
Atrioventricular block	1/1212 (0.1%)		0/1207 (0%)
Bradyarrhythmia	0/1212 (0%)		1/1207 (0.1%)
Cardiac discomfort	0/1212 (0%)		1/1207 (0.1%)
Cardiopulmonary failure	1/1212 (0.1%)		0/1207 (0%)
Intracardiac thrombus	1/1212 (0.1%)		0/1207 (0%)
Left ventricular dysfunction	0/1212 (0%)		1/1207 (0.1%)
Microvascular coronary artery disease	1/1212 (0.1%)		0/1207 (0%)
Myocardial fibrosis	1/1212 (0.1%)		0/1207 (0%)
Pericardial effusion	0/1212 (0%)		1/1207 (0.1%)
Pericarditis	0/1212 (0%)		1/1207 (0.1%)
Sinus node dysfunction	0/1212 (0%)		1/1207 (0.1%)
Sinus tachycardia	0/1212 (0%)		1/1207 (0.1%)
Tachycardia	0/1212 (0%)		1/1207 (0.1%)
Ventricular arrhythmia	0/1212 (0%)		1/1207 (0.1%)
Ventricular failure	0/1212 (0%)		1/1207 (0.1%)
Ear and labyrinth disorders
Vertigo	0/1212 (0%)		1/1207 (0.1%)
Vertigo positional	1/1212 (0.1%)		0/1207 (0%)
Eye disorders
Cataract	2/1212 (0.2%)		2/1207 (0.2%)
Glaucoma	0/1212 (0%)		3/1207 (0.2%)
Diabetic retinopathy	1/1212 (0.1%)		1/1207 (0.1%)
Detachment of retinal pigment epithelium	0/1212 (0%)		1/1207 (0.1%)
Eye haemorrhage	1/1212 (0.1%)		0/1207 (0%)
Hypotony of eye	0/1212 (0%)		1/1207 (0.1%)
Iris bombe	0/1212 (0%)		1/1207 (0.1%)
Posterior capsule opacification	0/1212 (0%)		1/1207 (0.1%)
Retinal detachment	0/1212 (0%)		1/1207 (0.1%)
Vitreous haemorrhage	0/1212 (0%)		1/1207 (0.1%)
Gastrointestinal disorders
Diarrhoea	33/1212 (2.7%)		25/1207 (2.1%)
Gastrointestinal haemorrhage	5/1212 (0.4%)		1/1207 (0.1%)
Abdominal pain	2/1212 (0.2%)		2/1207 (0.2%)
Gastritis erosive	2/1212 (0.2%)		2/1207 (0.2%)
Inguinal hernia	3/1212 (0.2%)		1/1207 (0.1%)
Duodenal ulcer	1/1212 (0.1%)		2/1207 (0.2%)
Anal fissure	2/1212 (0.2%)		0/1207 (0%)
Chronic gastritis	1/1212 (0.1%)		1/1207 (0.1%)
Gastric polyps	1/1212 (0.1%)		1/1207 (0.1%)
Gastritis	1/1212 (0.1%)		1/1207 (0.1%)
Haemorrhoids	1/1212 (0.1%)		1/1207 (0.1%)
Large intestine polyp	1/1212 (0.1%)		1/1207 (0.1%)
Pancreatitis acute	1/1212 (0.1%)		1/1207 (0.1%)
Vomiting	0/1212 (0%)		2/1207 (0.2%)
Abdominal hernia	1/1212 (0.1%)		0/1207 (0%)
Abdominal pain upper	0/1212 (0%)		1/1207 (0.1%)
Acute abdomen	0/1212 (0%)		1/1207 (0.1%)
Diabetic gastroparesis	1/1212 (0.1%)		0/1207 (0%)
Duodenal ulcer haemorrhage	1/1212 (0.1%)		0/1207 (0%)
Gastric ulcer haemorrhage	1/1212 (0.1%)		0/1207 (0%)
Gastrointestinal angiodysplasia	0/1212 (0%)		1/1207 (0.1%)
Gastrointestinal angiodysplasia haemorrhagic	0/1212 (0%)		1/1207 (0.1%)
Haemorrhagic erosive gastritis	0/1212 (0%)		1/1207 (0.1%)
Haemorrhoids thrombosed	0/1212 (0%)		1/1207 (0.1%)
Hiatus hernia	0/1212 (0%)		1/1207 (0.1%)
Ileus	1/1212 (0.1%)		0/1207 (0%)
Irritable bowel syndrome	0/1212 (0%)		1/1207 (0.1%)
Lower gastrointestinal haemorrhage	0/1212 (0%)		1/1207 (0.1%)
Nausea	0/1212 (0%)		1/1207 (0.1%)
Oesophageal obstruction	1/1212 (0.1%)		0/1207 (0%)
Pancreatitis	0/1212 (0%)		1/1207 (0.1%)
Peritoneal haemorrhage	1/1212 (0.1%)		0/1207 (0%)
Salivary gland calculus	1/1212 (0.1%)		0/1207 (0%)
Upper gastrointestinal haemorrhage	1/1212 (0.1%)		0/1207 (0%)
General disorders
Non-cardiac chest pain	10/1212 (0.8%)		12/1207 (1%)
Sudden death	2/1212 (0.2%)		6/1207 (0.5%)
Death	3/1212 (0.2%)		3/1207 (0.2%)
Sudden cardiac death	0/1212 (0%)		3/1207 (0.2%)
Pyrexia	2/1212 (0.2%)		0/1207 (0%)
Vascular stent restenosis	0/1212 (0%)		2/1207 (0.2%)
Chest pain	1/1212 (0.1%)		0/1207 (0%)
Exercise tolerance decreased	1/1212 (0.1%)		0/1207 (0%)
Oedema peripheral	1/1212 (0.1%)		0/1207 (0%)
Vascular stent occlusion	0/1212 (0%)		1/1207 (0.1%)
Vascular stent stenosis	1/1212 (0.1%)		0/1207 (0%)
Vascular stent thrombosis	1/1212 (0.1%)		0/1207 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/1212 (0.1%)		5/1207 (0.4%)
Bile duct stone	1/1212 (0.1%)		0/1207 (0%)
Cholangitis	0/1212 (0%)		1/1207 (0.1%)
Cholecystitis	0/1212 (0%)		1/1207 (0.1%)
Cholelithiasis	1/1212 (0.1%)		0/1207 (0%)
Hepatic cirrhosis	0/1212 (0%)		1/1207 (0.1%)
Hepatic lesion	1/1212 (0.1%)		0/1207 (0%)
Hepatitis acute	0/1212 (0%)		1/1207 (0.1%)
Hypertransaminasaemia	1/1212 (0.1%)		0/1207 (0%)
Liver disorder	0/1212 (0%)		1/1207 (0.1%)
Immune system disorders
Amyloidosis	0/1212 (0%)		1/1207 (0.1%)
Infections and infestations
Pneumonia	15/1212 (1.2%)		17/1207 (1.4%)
Urinary tract infection	6/1212 (0.5%)		3/1207 (0.2%)
Cellulitis	2/1212 (0.2%)		3/1207 (0.2%)
Bronchitis	2/1212 (0.2%)		4/1207 (0.3%)
Osteomyelitis	3/1212 (0.2%)		2/1207 (0.2%)
Gangrene	3/1212 (0.2%)		1/1207 (0.1%)
Sepsis	2/1212 (0.2%)		2/1207 (0.2%)
Septic shock	3/1212 (0.2%)		1/1207 (0.1%)
Upper respiratory tract infection	2/1212 (0.2%)		2/1207 (0.2%)
Viral infection	3/1212 (0.2%)		1/1207 (0.1%)
Diverticulitis	1/1212 (0.1%)		2/1207 (0.2%)
Ertsipelas	2/1212 (0.2%)		1/1207 (0.1%)
Gastroenteritis	2/1212 (0.2%)		1/1207 (0.1%)
Urosepsis	2/1212 (0.2%)		1/1207 (0.1%)
Diabetic gangrene	1/1212 (0.1%)		1/1207 (0.1%)
Escherichia urinary tract infection	2/1212 (0.2%)		0/1207 (0%)
Postoperative wound infection	2/1212 (0.2%)		0/1207 (0%)
Pyelonephritis	1/1212 (0.1%)		1/1207 (0.1%)
Subcutaneous abscess	0/1212 (0%)		2/1207 (0.2%)
Acute endocarditis	1/1212 (0.1%)		0/1207 (0%)
Anal abscess	0/1212 (0%)		1/1207 (0.1%)
Appendicitis	1/1212 (0.1%)		0/1207 (0%)
Appendicitis perforated	1/1212 (0.1%)		0/1207 (0%)
Brain abscess	1/1212 (0.1%)		0/1207 (0%)
Cholecystitis infective	1/1212 (0.1%)		0/1207 (0%)
Clostridium difficile colitis	0/1212 (0%)		1/1207 (0.1%)
Cystitis	1/1212 (0.1%)		0/1207 (0%)
Device related infection	1/1212 (0.1%)		0/1207 (0%)
Diabetic foot infection	0/1212 (0%)		1/1207 (0.1%)
Gallbladder empyema	1/1212 (0.1%)		0/1207 (0%)
Hepatitis E	1/1212 (0.1%)		0/1207 (0%)
Hepatitis viral	1/1212 (0.1%)		0/1207 (0%)
Herpes zoster	0/1212 (0%)		1/1207 (0.1%)
Localised infection	0/1212 (0%)		1/1207 (0.1%)
Lower respiratory tract infection	1/1212 (0.1%)		0/1207 (0%)
Lung infection	0/1212 (0%)		1/1207 (0.1%)
Mastoiditis	0/1212 (0%)		1/1207 (0.1%)
Mediastinitis	1/1212 (0.1%)		0/1207 (0%)
Necrotising fasciitis	0/1212 (0%)		1/1207 (0.1%)
Opportunistic infection	0/1212 (0%)		1/1207 (0.1%)
Pneumonia legionella	0/1212 (0%)		1/1207 (0.1%)
Pneumonia necrotising	1/1212 (0.1%)		0/1207 (0%)
Pneumonia streptococcal	0/1212 (0%)		1/1207 (0.1%)
Scrotal abscess	1/1212 (0.1%)		0/1207 (0%)
Soft tissue infection	0/1212 (0%)		1/1207 (0.1%)
Staphylococcal skin infection	0/1212 (0%)		1/1207 (0.1%)
Tooth abscess	0/1212 (0%)		1/1207 (0.1%)
Urinary tract infection bacterial	0/1212 (0%)		1/1207 (0.1%)
Urinary tract infection enterococcal	1/1212 (0.1%)		0/1207 (0%)
Syncope	1/1212 (0.1%)		5/1207 (0.4%)
Transient ischaemic attack	3/1212 (0.2%)		3/1207 (0.2%)
Injury, poisoning and procedural complications
Ankle fracture	1/1212 (0.1%)		1/1207 (0.1%)
Concussion	1/1212 (0.1%)		1/1207 (0.1%)
Coronary artery restenosis	1/1212 (0.1%)		1/1207 (0.1%)
Femur fracture	1/1212 (0.1%)		1/1207 (0.1%)
Forearm fracture	1/1212 (0.1%)		1/1207 (0.1%)
Hip fracture	2/1212 (0.2%)		0/1207 (0%)
Humerus fracture	1/1212 (0.1%)		1/1207 (0.1%)
Post procedural haematoma	1/1212 (0.1%)		1/1207 (0.1%)
Radius fracture	0/1212 (0%)		2/1207 (0.2%)
Subdural haematoma	1/1212 (0.1%)		1/1207 (0.1%)
Brain contusion	1/1212 (0.1%)		0/1207 (0%)
Facial bones fracture	1/1212 (0.1%)		0/1207 (0%)
Femoral neck fracture	1/1212 (0.1%)		0/1207 (0%)
Joint dislocation	0/1212 (0%)		1/1207 (0.1%)
Lumbosacral plexus injury	0/1212 (0%)		1/1207 (0.1%)
Nerve root injury	1/1212 (0.1%)		0/1207 (0%)
Post procedural haemorrhage	1/1212 (0.1%)		0/1207 (0%)
Postpericardiotomy syndrome	1/1212 (0.1%)		0/1207 (0%)
Pubis fracture	0/1212 (0%)		1/1207 (0.1%)
Radial head dislocation	0/1212 (0%)		1/1207 (0.1%)
Rib fracture	1/1212 (0.1%)		0/1207 (0%)
Road traffic accident	0/1212 (0%)		1/1207 (0.1%)
Skull fracture	0/1212 (0%)		1/1207 (0.1%)
Spinal compression fracture	0/1212 (0%)		1/1207 (0.1%)
Upper limb fracture	1/1212 (0.1%)		0/1207 (0%)
Vascular pseudoaneurysm	1/1212 (0.1%)		0/1207 (0%)
Wound	0/1212 (0%)		1/1207 (0.1%)
Investigations
Hepatic enzyme increased	3/1212 (0.2%)		0/1207 (0%)
Alanine aminotransferase increased	2/1212 (0.2%)		0/1207 (0%)
Blood creatine phosphokinase increased	1/1212 (0.1%)		0/1207 (0%)
Blood pressure abnormal	1/1212 (0.1%)		0/1207 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	6/1212 (0.5%)		5/1207 (0.4%)
Diabetes mellitus inadequate control	2/1212 (0.2%)		2/1207 (0.2%)
Hyperglycaemia	1/1212 (0.1%)		2/1207 (0.2%)
Hyperkalaemia	0/1212 (0%)		2/1207 (0.2%)
Metabolic disorder	1/1212 (0.1%)		1/1207 (0.1%)
Acidosis	0/1212 (0%)		1/1207 (0.1%)
Dehydration	0/1212 (0%)		1/1207 (0.1%)
Diabetic metabolic decompensation	0/1212 (0%)		1/1207 (0.1%)
Failure to thrive	0/1212 (0%)		1/1207 (0.1%)
Gout	0/1212 (0%)		1/1207 (0.1%)
Hypoglycaemia	1/1212 (0.1%)		0/1207 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	7/1212 (0.6%)		9/1207 (0.7%)
Spinal pain	0/1212 (0%)		3/1207 (0.2%)
Back pain	1/1212 (0.1%)		1/1207 (0.1%)
Intervertebral disc disorder	1/1212 (0.1%)		1/1207 (0.1%)
Intervertebral disc protrusion	1/1212 (0.1%)		1/1207 (0.1%)
Osteoarthritis	0/1212 (0%)		2/1207 (0.2%)
Spinal osteoarthritis	0/1212 (0%)		2/1207 (0.2%)
Ankylosing spondylitis	1/1212 (0.1%)		0/1207 (0%)
Joint swelling	0/1212 (0%)		1/1207 (0.1%)
Musculoskeletal pain	0/1212 (0%)		1/1207 (0.1%)
Neuropathic arthropathy	0/1212 (0%)		1/1207 (0.1%)
Osteochondrosis	1/1212 (0.1%)		0/1207 (0%)
Pathological fracture	0/1212 (0%)		1/1207 (0.1%)
Polymyalgia rheumatica	0/1212 (0%)		1/1207 (0.1%)
Rhabdomyolysis	0/1212 (0%)		1/1207 (0.1%)
Rotator cuff syndrome	1/1212 (0.1%)		0/1207 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	3/1212 (0.2%)		3/1207 (0.2%)
Lung neoplasm malignant	2/1212 (0.2%)		1/1207 (0.1%)
Adenocarcinoma of colon	1/1212 (0.1%)		1/1207 (0.1%)
Bladder cancer	2/1212 (0.2%)		0/1207 (0%)
Lung cancer metastatic	1/1212 (0.1%)		1/1207 (0.1%)
Metastases to liver	2/1212 (0.2%)		0/1207 (0%)
Non-Hodgkin's lymphoma	1/1212 (0.1%)		1/1207 (0.1%)
Pancreatic carcinoma metastatic	1/1212 (0.1%)		1/1207 (0.1%)
Renal cancer	1/1212 (0.1%)		1/1207 (0.1%)
Benign hepatic neoplasm	0/1212 (0%)		1/1207 (0.1%)
Benign neoplasm of bladder	1/1212 (0.1%)		0/1207 (0%)
Bladder neoplasm	0/1212 (0%)		1/1207 (0.1%)
Bladder transitional cell carcinoma	1/1212 (0.1%)		0/1207 (0%)
Brain cancer metastatic	1/1212 (0.1%)		0/1207 (0%)
Breast cancer	0/1212 (0%)		1/1207 (0.1%)
Bronchial carcinoma	1/1212 (0.1%)		0/1207 (0%)
Colon adenoma	0/1212 (0%)		1/1207 (0.1%)
Gastrointestinal stromal tumour	0/1212 (0%)		1/1207 (0.1%)
Intraductal proliferative breast lesion	0/1212 (0%)		1/1207 (0.1%)
Invasive ductal breast carcinoma	1/1212 (0.1%)		0/1207 (0%)
Laryngeal cancer	1/1212 (0.1%)		0/1207 (0%)
Lung adenocarcinoma	0/1212 (0%)		1/1207 (0.1%)
Lung squamous cell carcinoma metastatic	1/1212 (0.1%)		0/1207 (0%)
Malignant neoplasm of unknown primary site	0/1212 (0%)		1/1207 (0.1%)
Metastases to bone	1/1212 (0.1%)		0/1207 (0%)
Metastases to central nervous system	0/1212 (0%)		1/1207 (0.1%)
Metastases to lung	1/1212 (0.1%)		0/1207 (0%)
Metastases to spine	0/1212 (0%)		1/1207 (0.1%)
Nasopharyngeal cancer	0/1212 (0%)		1/1207 (0.1%)
Neuroendocrine tumour	0/1212 (0%)		1/1207 (0.1%)
Non-small cell lung cancer stage IV	1/1212 (0.1%)		0/1207 (0%)
Oesophageal adenocarcinoma	0/1212 (0%)		1/1207 (0.1%)
Oropharyngeal squamous cell carcinoma	0/1212 (0%)		1/1207 (0.1%)
Ovarian cancer stage IV	1/1212 (0.1%)		0/1207 (0%)
Ovarian fibroma	0/1212 (0%)		1/1207 (0.1%)
Pancreatic carcinoma	1/1212 (0.1%)		0/1207 (0%)
Paraneoplastic syndrome	0/1212 (0%)		1/1207 (0.1%)
Rectal adenocarcinoma	1/1212 (0.1%)		0/1207 (0%)
Rectal cancer	0/1212 (0%)		1/1207 (0.1%)
Rectosigmoid cancer	0/1212 (0%)		1/1207 (0.1%)
Renal cancer metastatic	0/1212 (0%)		1/1207 (0.1%)
Small cell carcinoma	1/1212 (0.1%)		0/1207 (0%)
Small cell lung cancer	0/1212 (0%)		1/1207 (0.1%)
Squamous cell carcinoma of lung	1/1212 (0.1%)		0/1207 (0%)
Thyroid adenoma	0/1212 (0%)		1/1207 (0.1%)
Transitional cell carcinoma	0/1212 (0%)		1/1207 (0.1%)
Uterine neoplasm	1/1212 (0.1%)		0/1207 (0%)
Nervous system disorders
Ischaemic stroke	5/1212 (0.4%)		5/1207 (0.4%)
Cerebrovascular accident	4/1212 (0.3%)		2/1207 (0.2%)
Carotid artery stenosis	2/1212 (0.2%)		2/1207 (0.2%)
Cerebral infarction	2/1212 (0.2%)		2/1207 (0.2%)
Haemorrhagic stroke	1/1212 (0.1%)		1/1207 (0.1%)
Quadriparesis	2/1212 (0.2%)		0/1207 (0%)
VIIth nerve paralysis	1/1212 (0.1%)		1/1207 (0.1%)
Brain stem stroke	0/1212 (0%)		1/1207 (0.1%)
Carotid sinus syndrome	1/1212 (0.1%)		0/1207 (0%)
Carpal tunnel syndrome	0/1212 (0%)		1/1207 (0.1%)
Cerebral arteriosclerosis	0/1212 (0%)		1/1207 (0.1%)
Cervical cord compression	1/1212 (0.1%)		0/1207 (0%)
Diabetic neuropathy	0/1212 (0%)		1/1207 (0.1%)
Dizziness	0/1212 (0%)		1/1207 (0.1%)
Dysarthria	1/1212 (0.1%)		0/1207 (0%)
Febrile convulsion	1/1212 (0.1%)		0/1207 (0%)
Guillain-Barre syndrome	0/1212 (0%)		1/1207 (0.1%)
Hypoaesthesia	0/1212 (0%)		1/1207 (0.1%)
Intracranial aneurysm	1/1212 (0.1%)		0/1207 (0%)
Lumbar radiculopathy	1/1212 (0.1%)		0/1207 (0%)
Lumbosacral radiculopathy	1/1212 (0.1%)		0/1207 (0%)
Nerve compression	1/1212 (0.1%)		0/1207 (0%)
Paraesthesia	0/1212 (0%)		1/1207 (0.1%)
Parkinson's disease	1/1212 (0.1%)		0/1207 (0%)
Polyneuropathy	0/1212 (0%)		1/1207 (0.1%)
Psychomotor hyperactivity	1/1212 (0.1%)		0/1207 (0%)
Seizure	1/1212 (0.1%)		0/1207 (0%)
Subarachnoid haemorrhage	0/1212 (0%)		1/1207 (0.1%)
Vertebrobasilar insufficiency	0/1212 (0%)		1/1207 (0.1%)
Psychiatric disorders
Depression	1/1212 (0.1%)		1/1207 (0.1%)
Anxiety	0/1212 (0%)		1/1207 (0.1%)
Anxiety disorder	1/1212 (0.1%)		0/1207 (0%)
Completed suicide	0/1212 (0%)		1/1207 (0.1%)
Confusional state	1/1212 (0.1%)		0/1207 (0%)
Suicidal ideation	1/1212 (0.1%)		0/1207 (0%)
Suicide attempt	0/1212 (0%)		1/1207 (0.1%)
Renal and urinary disorders
Acute kidney injury	9/1212 (0.7%)		7/1207 (0.6%)
Chronic kidney disease	4/1212 (0.3%)		3/1207 (0.2%)
Nephrolithiasis	2/1212 (0.2%)		2/1207 (0.2%)
Renal failure	2/1212 (0.2%)		2/1207 (0.2%)
Calculus ureteric	2/1212 (0.2%)		1/1207 (0.1%)
Ureteric stenosis	1/1212 (0.1%)		2/1207 (0.2%)
Diabetic nephropathy	0/1212 (0%)		2/1207 (0.2%)
Urinary retention	0/1212 (0%)		2/1207 (0.2%)
Azotaemia	0/1212 (0%)		1/1207 (0.1%)
Bladder perforation	1/1212 (0.1%)		0/1207 (0%)
Calculus bladder	1/1212 (0.1%)		0/1207 (0%)
Calculus urinary	0/1212 (0%)		1/1207 (0.1%)
Haematuria	1/1212 (0.1%)		0/1207 (0%)
Hydronephrosis	0/1212 (0%)		1/1207 (0.1%)
Nephropathy	1/1212 (0.1%)		0/1207 (0%)
Renal artery stenosis	0/1212 (0%)		1/1207 (0.1%)
Renal mass	1/1212 (0.1%)		0/1207 (0%)
Ureteric rupture	1/1212 (0.1%)		0/1207 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/1212 (0.2%)		1/1207 (0.1%)
Cervical dysplasia	0/1212 (0%)		1/1207 (0.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	6/1212 (0.5%)		5/1207 (0.4%)
Epistaxis	4/1212 (0.3%)		1/1207 (0.1%)
Pulmonary embolism	1/1212 (0.1%)		3/1207 (0.2%)
Pulmonary oedema	1/1212 (0.1%)		2/1207 (0.2%)
Acute respiratory failure	1/1212 (0.1%)		1/1207 (0.1%)
Acute pulmonary oedema	1/1212 (0.1%)		0/1207 (0%)
Bronchial haemorrhage	0/1212 (0%)		1/1207 (0.1%)
Bronchiectasis	1/1212 (0.1%)		0/1207 (0%)
Dyspnoea	1/1212 (0.1%)		0/1207 (0%)
Haemoptysis	0/1212 (0%)		1/1207 (0.1%)
Hiccups	1/1212 (0.1%)		0/1207 (0%)
Nasal polyps	1/1212 (0.1%)		0/1207 (0%)
Obstructive airways disorder	1/1212 (0.1%)		0/1207 (0%)
Paranasal sinus haematoma	1/1212 (0.1%)		0/1207 (0%)
Pleural effusion	1/1212 (0.1%)		0/1207 (0%)
Pulmonary congestion	0/1212 (0%)		1/1207 (0.1%)
Sinus polyp	1/1212 (0.1%)		0/1207 (0%)
Tracheal stenosis	1/1212 (0.1%)		0/1207 (0%)
Vocal cord cyst	0/1212 (0%)		1/1207 (0.1%)
Skin and subcutaneous tissue disorders
Diabetic foot	2/1212 (0.2%)		2/1207 (0.2%)
Pemphigoid	1/1212 (0.1%)		0/1207 (0%)
Surgical and medical procedures
Medical device removal	0/1212 (0%)		1/1207 (0.1%)
Vascular disorders
Peripheral arterial occlusive disease	7/1212 (0.6%)		7/1207 (0.6%)
Hypertension	2/1212 (0.2%)		9/1207 (0.7%)
Hypertensive crisis	1/1212 (0.1%)		7/1207 (0.6%)
Hypertensive emergency	2/1212 (0.2%)		2/1207 (0.2%)
Aortic stenosis	1/1212 (0.1%)		2/1207 (0.2%)
Peripheral ischaemia	2/1212 (0.2%)		1/1207 (0.1%)
Hypotension	2/1212 (0.2%)		0/1207 (0%)
Hypovolaemic shock	1/1212 (0.1%)		1/1207 (0.1%)
Arteriosclerosis	1/1212 (0.1%)		0/1207 (0%)
Deep vein thrombosis	0/1212 (0%)		1/1207 (0.1%)
Extremity necrosis	0/1212 (0%)		1/1207 (0.1%)
Haematoma	0/1212 (0%)		1/1207 (0.1%)
Ischaemia	1/1212 (0.1%)		0/1207 (0%)
Orthostatic hypotension	1/1212 (0.1%)		0/1207 (0%)
Peripheral artery stenosis	1/1212 (0.1%)		0/1207 (0%)
Peripheral artery thrombosis	1/1212 (0.1%)		0/1207 (0%)
Subclavian artery occlusion	0/1212 (0%)		1/1207 (0.1%)
Other (Not Including Serious) Adverse Events
	High-Intensity Statin Therapy+RVX000222		High-Intensity Statin Therapy+Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	830/1212 (68.5%)		820/1207 (67.9%)
Blood and lymphatic system disorders
Anemia	36/1212 (3%)		40/1207 (3.3%)
Cardiac disorders
Angina	74/1212 (6.1%)		76/1207 (6.3%)
Angina unstable	58/1212 (4.8%)		41/1207 (3.4%)
Acute myocardial infarction	42/1212 (3.5%)		50/1207 (4.1%)
Cardiac failure	22/1212 (1.8%)		38/1207 (3.1%)
Gastrointestinal disorders
Diarrhoea	43/1212 (3.5%)		44/1207 (3.6%)
Abdominal pain	12/1212 (1%)		24/1207 (2%)
Nausea	26/1212 (2.1%)		7/1207 (0.6%)
Hepatobiliary	24/1212 (2%)		42/1207 (3.5%)
General disorders
Non-cardiac chest pain	33/1212 (2.7%)		39/1207 (3.2%)
Infections and infestations
Nasopharyngitis	46/1212 (3.8%)		56/1207 (4.6%)
Urinary tract infection	58/1212 (4.8%)		40/1207 (3.3%)
Influenza	43/1212 (3.5%)		47/1207 (3.9%)
Bronchitis	25/1212 (2.1%)		32/1207 (2.7%)
Pneumonia	27/1212 (2.2%)		26/1207 (2.2%)
Upper respiratory tract infection	29/1212 (2.4%)		24/1207 (2%)
Investigations
ALT increase	64/1212 (5.3%)		18/1207 (1.5%)
Metabolism and nutrition disorders
Worsening diabetes mellitus	93/1212 (7.7%)		93/1207 (7.7%)
Musculoskeletal and connective tissue disorders
Myalgia	37/1212 (3.1%)		33/1207 (2.7%)
Back pain	27/1212 (2.2%)		28/1207 (2.3%)
Pain in extremity	15/1212 (1.2%)		26/1207 (2.2%)
Arthralgia	11/1212 (0.9%)		24/1207 (2%)
Vascular disorders
Hypertension	72/1212 (5.9%)		72/1207 (6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.