Coronary Artery Disease, Diabetes Mellitus, Type 2
Conditions
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.
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.
Interventions
DRUGApabetalone
100 mg capsule
DRUGPlacebo
Capsule manufactured to mimic RVX000222 100 mg capsule
DRUGAtorvastatin
High-Intensity Statin
DRUGRosuvastatin
High-Intensity Statin
Sponsors
PPD Development, LP
ICON plc
Medidata Solutions
Resverlogix Corp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Hospitalization for Congestive Heart Failure (CHF) | 120 weeks | — |
| Incidence of All-cause Mortality | 120 weeks | — |
| Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
| Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
| Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
| Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
| 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. |
| Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
| Change in Glucose From Baseline Over Time Between and Within Treatment Groups | 120 weeks | — |
| Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | 172 weeks | — |
| Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | 52 weeks | — |
| 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 | — |
| Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | 120 weeks | — |
Countries
Argentina, Australia, Belgium, Bulgaria, Croatia, Germany, Hungary, Israel, Mexico, Netherlands, Poland, Russia, Serbia, Slovakia, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Intensity Statin Therapy+RVX000222 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 | 1,212 |
| High-Intensity Statin Therapy+Placebo 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 | 1,206 |
| Total | 2,418 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 61 | 72 |
| Overall Study | Lost to Follow-up | 7 | 13 |
| Overall Study | Other reasons | 26 | 15 |
| Overall Study | Withdrawal by Subject | 31 | 24 |
Baseline characteristics
| Characteristic | High-Intensity Statin Therapy+RVX000222 | High-Intensity Statin Therapy+Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.0 years | 62.0 years | 62.0 years |
| Age, Customized ≤65 years | 816 Participants | 772 Participants | 1588 Participants |
| Age, Customized >65 years | 396 Participants | 434 Participants | 830 Participants |
| Body-mass index (BMI) | 29.589 kg/m2 | 29.585 kg/m2 | 29.585 kg/m2 |
| Body weight | 85.75 kilograms (kg) | 85.90 kilograms (kg) | 85.90 kilograms (kg) |
| Race (NIH/OMB) American Indian or Alaska Native | 27 Participants | 31 Participants | 58 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 19 Participants | 39 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 102 Participants | 100 Participants | 202 Participants |
| Race (NIH/OMB) White | 1063 Participants | 1056 Participants | 2119 Participants |
| Sex: Female, Male Female | 305 Participants | 313 Participants | 618 Participants |
| Sex: Female, Male Male | 907 Participants | 893 Participants | 1800 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 61 / 1,212 | 72 / 1,207 |
| other Total, other adverse events | 830 / 1,212 | 820 / 1,207 |
| serious Total, serious adverse events | 354 / 1,212 | 339 / 1,207 |
Outcome results
Primary
Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | CV Death | 34 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | Non-fatal MI | 76 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | Stroke | 15 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | CV Death | 42 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | Non-fatal MI | 92 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE | Stroke | 15 events |
p-value: 0.10795% CI: [0.649, 1.044]Stratified long-rank
Secondary
Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups
Time frame: 172 weeks
Population: Subject data is missing across time points
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 5 (Week 6) | 70.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 70.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 10 (Week 20) | 68.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 17 (Week 88) | 72.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 7 (Week 10) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 72.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 68.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 22 (Week 148) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 4 (Week 4) | 70.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 23 (Week 160) | 68.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 12 (Week 28) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 24 (Week 172) | 75.5 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 8 (Week 12) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 72.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 13 (Week 40) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Follow-up | 76.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 6 (Week 8) | 69.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Baseline | 78.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 71.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 19 (Week 112) | 71.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 9 (Week 16) | 68.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 20 (Week 124) | 71.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 15 (Week 64) | 71.0 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 21 (Week 136) | 69.5 U/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 3 (Week 2) | 71.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 21 (Week 136) | 77.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 3 (Week 2) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 4 (Week 4) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 5 (Week 6) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 6 (Week 8) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 7 (Week 10) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 8 (Week 12) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 9 (Week 16) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 10 (Week 20) | 74.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 12 (Week 28) | 74.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 13 (Week 40) | 74.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 15 (Week 64) | 74.5 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 17 (Week 88) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 22 (Week 148) | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 23 (Week 160) | 78.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 24 (Week 172) | 83.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 77.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Follow-up | 76.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Baseline | 77.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 19 (Week 112) | 75.0 U/L |
| High-Intensity Statin Therapy+Placebo | Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups | Visit 20 (Week 124) | 77.0 U/L |
Secondary
Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: A select subset of subjects were analyzed for ApoA-I, Subject data is missing across time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 129.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 131.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 132.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 128.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 131.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 132.5 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 119.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 127.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 117.5 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 125.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 124.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 129.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 125.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 125.0 mg/dL |
Secondary
Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: A select subset of subjects were analyzed for ApoB, Subject data is missing across time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 66.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 70.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 70.0 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 70.5 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 68.5 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 70.5 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 68.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 72.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 72.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 71.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 66.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 68.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 68.0 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 69.0 mg/dL |
Secondary
Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 52 weeks
Population: A select subset of subjects in two countries were analyzed for CRP, Subject data is missing across time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 2.875 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 8 (Week 12) | 1.755 mg/dL |
| High-Intensity Statin Therapy+RVX000222 | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.710 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 2.740 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 8 (Week 12) | 1.805 mg/dL |
| High-Intensity Statin Therapy+Placebo | Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.580 mg/dL |
Secondary
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
Population: Subject data is missing across time points
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | 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) | Visit 18 (Week 100) | 46.5 ml/min |
| High-Intensity Statin Therapy+RVX000222 | 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) | Visit 11 (Week 24) | 53.0 ml/min |
| High-Intensity Statin Therapy+RVX000222 | 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) | Visit 14 (Week 52) | 52.4 ml/min |
| High-Intensity Statin Therapy+RVX000222 | 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) | LVT | 52.5 ml/min |
| High-Intensity Statin Therapy+RVX000222 | 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) | Visit 16 (Week 76) | 50.8 ml/min |
| High-Intensity Statin Therapy+RVX000222 | 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) | Baseline | 51.4 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | Visit 16 (Week 76) | 54.8 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | Baseline | 48.9 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | Visit 18 (Week 100) | 56.7 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | LVT | 53.9 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | Visit 11 (Week 24) | 53.3 ml/min |
| High-Intensity Statin Therapy+Placebo | 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) | Visit 14 (Week 52) | 52.5 ml/min |
Secondary
Change in Glucose From Baseline Over Time Between and Within Treatment Groups
Time frame: 120 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 14 (Week 52) | 7.900 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 18 (Week 100) | 8.010 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 11 (Week 24) | 7.925 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | LVT | 8.100 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 16 (Week 76) | 7.920 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Follow-up | 7.650 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Baseline | 7.590 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Follow-up | 7.595 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Baseline | 7.385 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 11 (Week 24) | 7.835 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 14 (Week 52) | 7.800 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 16 (Week 76) | 7.840 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | Visit 18 (Week 100) | 7.890 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Glucose From Baseline Over Time Between and Within Treatment Groups | LVT | 7.795 mmol/L |
Secondary
Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 1.010 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 0.970 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 0.970 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 0.960 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 0.970 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 0.990 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 0.870 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 0.910 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 0.950 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 0.860 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 0.920 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 0.940 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 0.960 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 0.930 mmol/L |
Secondary
Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | LVT | 7.40 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Follow-up | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Baseline | 7.40 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 7.20 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+RVX000222 | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 18 (Week 100) | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 7.20 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | LVT | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 16 (Week 76) | 7.40 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Follow-up | 7.20 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 7.30 % of hemoglobin |
| High-Intensity Statin Therapy+Placebo | Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups | Baseline | 7.30 % of hemoglobin |
Secondary
Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.590 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 1.660 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 1.530 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 1.700 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 1.600 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 1.650 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 1.690 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 1.680 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 1.690 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 1.530 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.655 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 1.660 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 1.725 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 1.745 mmol/L |
Secondary
Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups
Time frame: 120 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.735 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 1.755 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 1.660 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 1.700 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 1.730 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 1.650 mmol/L |
| High-Intensity Statin Therapy+RVX000222 | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 1.630 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Follow-up | 1.720 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Baseline | 1.690 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 11 (Week 24) | 1.670 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 14 (Week 52) | 1.700 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 16 Week 76) | 1.670 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Visit 18 Week 100) | 1.610 mmol/L |
| High-Intensity Statin Therapy+Placebo | Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups | Last Visit on Treatment (LVT) | 1.650 mmol/L |
Secondary
Incidence of All-cause Mortality
Time frame: 120 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Incidence of All-cause Mortality | 61 Participants |
| High-Intensity Statin Therapy+Placebo | Incidence of All-cause Mortality | 72 Participants |
p-value: 0.4495% CI: [0.62, 1.24]Stratified long-rank
Secondary
Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Hospitalization for CVD events | 22 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Non-fatal MI | 74 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Stroke | 15 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | CV Death | 33 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Stroke | 15 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Non-fatal MI | 91 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | CV Death | 42 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE | Hospitalization for CVD events | 18 events |
p-value: 0.149595% CI: [0.679, 1.061]Stratified long-rank
Secondary
Incidence of Hospitalization for Congestive Heart Failure (CHF)
Time frame: 120 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Incidence of Hospitalization for Congestive Heart Failure (CHF) | 29 events |
| High-Intensity Statin Therapy+Placebo | Incidence of Hospitalization for Congestive Heart Failure (CHF) | 48 events |
p-value: 0.0395% CI: [0.38, 0.94]Stratified long-rank
Post Hoc
Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | CV Death (CVD) | 45 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | Non-fatal MI | 77 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | Stroke | 17 events |
| High-Intensity Statin Therapy+RVX000222 | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | First Hospitalization for CHF | 29 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | First Hospitalization for CHF | 48 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | CV Death (CVD) | 55 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | Stroke | 17 events |
| High-Intensity Statin Therapy+Placebo | Incidence of First Occurrence of Adjudication-Confirmed Four-Point MACE | Non-fatal MI | 94 events |
p-value: 0.0395% CI: [0.63, 0.98]Log Rank