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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02586155




Registration number
NCT02586155
Ethics application status
Date submitted
21/10/2015
Date registered
26/10/2015

Titles & IDs
Public title
Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD
Scientific 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)
Secondary ID [1] 0 0
RVX222-CS-015
Universal Trial Number (UTN)
Trial acronym
BETonMACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Coronary Artery Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Apabetalone
Treatment: Drugs - Placebo
Treatment: Drugs - Atorvastatin
Treatment: Drugs - Rosuvastatin

Experimental: High-Intensity statin therapy+RVX000222 - Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)

Active comparator: High-Intensity statin therapy+Placebo - Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)


Treatment: Drugs: Apabetalone
100 mg capsule

Treatment: Drugs: Placebo
Capsule manufactured to mimic RVX000222 100 mg capsule

Treatment: Drugs: Atorvastatin
High-Intensity Statin

Treatment: Drugs: Rosuvastatin
High-Intensity Statin
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE
Timepoint [1] 0 0
120 weeks
Secondary outcome [1] 0 0
Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE
Timepoint [1] 0 0
120 weeks
Secondary outcome [2] 0 0
Incidence of Hospitalization for Congestive Heart Failure (CHF)
Timepoint [2] 0 0
120 weeks
Secondary outcome [3] 0 0
Incidence of All-cause Mortality
Timepoint [3] 0 0
120 weeks
Secondary outcome [4] 0 0
Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [4] 0 0
120 weeks
Secondary outcome [5] 0 0
Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [5] 0 0
120 weeks
Secondary outcome [6] 0 0
Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [6] 0 0
120 weeks
Secondary outcome [7] 0 0
Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [7] 0 0
120 weeks
Secondary outcome [8] 0 0
Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [8] 0 0
120 weeks
Secondary outcome [9] 0 0
Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups
Timepoint [9] 0 0
120 weeks
Secondary outcome [10] 0 0
Change in Glucose From Baseline Over Time Between and Within Treatment Groups
Timepoint [10] 0 0
120 weeks
Secondary outcome [11] 0 0
Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups
Timepoint [11] 0 0
172 weeks
Secondary outcome [12] 0 0
Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups
Timepoint [12] 0 0
52 weeks
Secondary outcome [13] 0 0
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)
Timepoint [13] 0 0
120 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/06/2021
Sample size
Target
Accrual to date
Final
2425
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Bahía Blanca
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
Coronel Suárez
Country [4] 0 0
Argentina
State/province [4] 0 0
Corrientes
Country [5] 0 0
Argentina
State/province [5] 0 0
Córdoba
Country [6] 0 0
Argentina
State/province [6] 0 0
Haedo
Country [7] 0 0
Argentina
State/province [7] 0 0
Lanús
Country [8] 0 0
Argentina
State/province [8] 0 0
Mar Del Plata
Country [9] 0 0
Argentina
State/province [9] 0 0
Mendoza
Country [10] 0 0
Argentina
State/province [10] 0 0
Ramos Mejia
Country [11] 0 0
Argentina
State/province [11] 0 0
Rosario
Country [12] 0 0
Argentina
State/province [12] 0 0
Salta
Country [13] 0 0
Argentina
State/province [13] 0 0
San Isidro
Country [14] 0 0
Argentina
State/province [14] 0 0
San Miguel De Tucumán
Country [15] 0 0
Argentina
State/province [15] 0 0
Santa Fe
Country [16] 0 0
Argentina
State/province [16] 0 0
Santiago Del Estero
Country [17] 0 0
Argentina
State/province [17] 0 0
Villa María
Country [18] 0 0
Argentina
State/province [18] 0 0
Zárate
Country [19] 0 0
Belgium
State/province [19] 0 0
Antwerpen
Country [20] 0 0
Belgium
State/province [20] 0 0
Bonheiden
Country [21] 0 0
Belgium
State/province [21] 0 0
Turnhout
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Gabrovo
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Lovech
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Pazardzhik
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Pleven
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Smolyan
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Sofia
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Stara Zagora
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Varna
Country [30] 0 0
Croatia
State/province [30] 0 0
Karlovac
Country [31] 0 0
Croatia
State/province [31] 0 0
Krapinske Toplice
Country [32] 0 0
Croatia
State/province [32] 0 0
Osijek
Country [33] 0 0
Croatia
State/province [33] 0 0
Slavonski Brod
Country [34] 0 0
Croatia
State/province [34] 0 0
Virovitica
Country [35] 0 0
Croatia
State/province [35] 0 0
Zagreb
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Germany
State/province [37] 0 0
Chemnitz
Country [38] 0 0
Germany
State/province [38] 0 0
Dresden
Country [39] 0 0
Germany
State/province [39] 0 0
Erfurt
Country [40] 0 0
Germany
State/province [40] 0 0
Heidelberg
Country [41] 0 0
Germany
State/province [41] 0 0
Hoyerswerda
Country [42] 0 0
Germany
State/province [42] 0 0
Kassel
Country [43] 0 0
Germany
State/province [43] 0 0
Langen
Country [44] 0 0
Germany
State/province [44] 0 0
Leverkusen
Country [45] 0 0
Hungary
State/province [45] 0 0
Baja
Country [46] 0 0
Hungary
State/province [46] 0 0
Berettyóújfalu
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
Country [48] 0 0
Hungary
State/province [48] 0 0
Komárom
Country [49] 0 0
Hungary
State/province [49] 0 0
Mosonmagyaróvár
Country [50] 0 0
Hungary
State/province [50] 0 0
Nagykanizsa
Country [51] 0 0
Hungary
State/province [51] 0 0
Pécs
Country [52] 0 0
Hungary
State/province [52] 0 0
Szeged
Country [53] 0 0
Hungary
State/province [53] 0 0
Szekszárd
Country [54] 0 0
Hungary
State/province [54] 0 0
Székesfehérvár
Country [55] 0 0
Israel
State/province [55] 0 0
Ashkelon
Country [56] 0 0
Israel
State/province [56] 0 0
Be'er Sheva
Country [57] 0 0
Israel
State/province [57] 0 0
Hadera
Country [58] 0 0
Israel
State/province [58] 0 0
Haifa
Country [59] 0 0
Israel
State/province [59] 0 0
Holon
Country [60] 0 0
Israel
State/province [60] 0 0
Jerusalem
Country [61] 0 0
Israel
State/province [61] 0 0
Kefar-Sava
Country [62] 0 0
Israel
State/province [62] 0 0
Nahariya
Country [63] 0 0
Israel
State/province [63] 0 0
Nazareth
Country [64] 0 0
Israel
State/province [64] 0 0
Ramat Gan
Country [65] 0 0
Israel
State/province [65] 0 0
Rehovot
Country [66] 0 0
Israel
State/province [66] 0 0
Safed
Country [67] 0 0
Israel
State/province [67] 0 0
Tel Aviv
Country [68] 0 0
Israel
State/province [68] 0 0
Tel-Aviv
Country [69] 0 0
Israel
State/province [69] 0 0
Tiberias
Country [70] 0 0
Mexico
State/province [70] 0 0
Aguascalientes
Country [71] 0 0
Mexico
State/province [71] 0 0
Chihuahua
Country [72] 0 0
Mexico
State/province [72] 0 0
Ciudad de México
Country [73] 0 0
Mexico
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Ciudad De México
Country [74] 0 0
Mexico
State/province [74] 0 0
Culiacan
Country [75] 0 0
Mexico
State/province [75] 0 0
Durango
Country [76] 0 0
Mexico
State/province [76] 0 0
Guadalajara
Country [77] 0 0
Mexico
State/province [77] 0 0
León De Los Aldama
Country [78] 0 0
Mexico
State/province [78] 0 0
Merida
Country [79] 0 0
Mexico
State/province [79] 0 0
Mexico City
Country [80] 0 0
Mexico
State/province [80] 0 0
Monclova
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Mexico
State/province [81] 0 0
Monterrey
Country [82] 0 0
Mexico
State/province [82] 0 0
Pachuca
Country [83] 0 0
Mexico
State/province [83] 0 0
San Luis Potosi
Country [84] 0 0
Mexico
State/province [84] 0 0
San Luis Potosí
Country [85] 0 0
Mexico
State/province [85] 0 0
Toluca
Country [86] 0 0
Mexico
State/province [86] 0 0
Veracruz
Country [87] 0 0
Mexico
State/province [87] 0 0
Zapopan
Country [88] 0 0
Netherlands
State/province [88] 0 0
Amersfoort
Country [89] 0 0
Netherlands
State/province [89] 0 0
Amsterdam
Country [90] 0 0
Poland
State/province [90] 0 0
Bialystok
Country [91] 0 0
Poland
State/province [91] 0 0
Chrzanow
Country [92] 0 0
Poland
State/province [92] 0 0
Dabrowa Gornicza
Country [93] 0 0
Poland
State/province [93] 0 0
Gdynia
Country [94] 0 0
Poland
State/province [94] 0 0
Kielce
Country [95] 0 0
Poland
State/province [95] 0 0
Kraków
Country [96] 0 0
Poland
State/province [96] 0 0
Lodz
Country [97] 0 0
Poland
State/province [97] 0 0
Lódz
Country [98] 0 0
Poland
State/province [98] 0 0
Nysa
Country [99] 0 0
Poland
State/province [99] 0 0
Opole
Country [100] 0 0
Poland
State/province [100] 0 0
Oswiecim
Country [101] 0 0
Poland
State/province [101] 0 0
Otwock
Country [102] 0 0
Poland
State/province [102] 0 0
Plock
Country [103] 0 0
Poland
State/province [103] 0 0
Tarnobrzeg
Country [104] 0 0
Poland
State/province [104] 0 0
Warszawa
Country [105] 0 0
Poland
State/province [105] 0 0
Wroclaw
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Chelyabinsk
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Ekaterinburg
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Kemerovo
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Krasnodar
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Moscow
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Nizhniy Novgorod
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Novosibirsk
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Petrozavodsk
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Rostov-on-Don
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Saint Petersburg
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Saratov
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Sochi
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Tomsk
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Vladimir
Country [120] 0 0
Serbia
State/province [120] 0 0
Belgrade
Country [121] 0 0
Serbia
State/province [121] 0 0
Kragujevac
Country [122] 0 0
Serbia
State/province [122] 0 0
Niska Banja
Country [123] 0 0
Serbia
State/province [123] 0 0
Nis
Country [124] 0 0
Serbia
State/province [124] 0 0
Novi Sad
Country [125] 0 0
Serbia
State/province [125] 0 0
Sremska Kamenica
Country [126] 0 0
Serbia
State/province [126] 0 0
Uzice
Country [127] 0 0
Serbia
State/province [127] 0 0
Zajecar
Country [128] 0 0
Slovakia
State/province [128] 0 0
Bardejov
Country [129] 0 0
Slovakia
State/province [129] 0 0
Bratislava
Country [130] 0 0
Slovakia
State/province [130] 0 0
Dolny Kubin
Country [131] 0 0
Slovakia
State/province [131] 0 0
Kosice
Country [132] 0 0
Slovakia
State/province [132] 0 0
Lucenec
Country [133] 0 0
Slovakia
State/province [133] 0 0
Moldava nad Bodvou
Country [134] 0 0
Slovakia
State/province [134] 0 0
Nove Mesto nad Vahom
Country [135] 0 0
Slovakia
State/province [135] 0 0
Nove Zamky
Country [136] 0 0
Slovakia
State/province [136] 0 0
Roznava
Country [137] 0 0
Slovakia
State/province [137] 0 0
Zilina
Country [138] 0 0
Taiwan
State/province [138] 0 0
Changhua
Country [139] 0 0
Taiwan
State/province [139] 0 0
Kaohsiung
Country [140] 0 0
Taiwan
State/province [140] 0 0
New Taipei City
Country [141] 0 0
Taiwan
State/province [141] 0 0
Taichung
Country [142] 0 0
Taiwan
State/province [142] 0 0
Tainan City
Country [143] 0 0
Taiwan
State/province [143] 0 0
Taipei City
Country [144] 0 0
Taiwan
State/province [144] 0 0
Taipei
Country [145] 0 0
Taiwan
State/province [145] 0 0
Taoyuan City

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Resverlogix Corp
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
PPD
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
ICON plc
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Medidata Solutions
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kausik Ray, MD
Address 0 0
Imperial College London
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Ray KK, Nicholls SJ, Buhr KA, Ginsberg HN, Johanss... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT02586155