Dyslipidemia, Type2 Diabetes
Conditions
Brief summary
The primary objective of the study is to determine whether pemafibrate administered twice daily will delay the time to first occurrence of any component of the clinical composite endpoint of: * nonfatal Myocardial Infarction (MI) * nonfatal ischemic stroke * coronary revascularization; or * Cardio Vascular (CV) death.
Detailed description
A multi-regional clinical trial with participating sites in the following countries. India is being conducted under a previous protocol version due to regulatory requirements. * Argentina * Brazil * Bulgaria * Canada * Colombia * Czech Republic * Denmark * France * Germany * Hungary * India * Israel * Japan * Mexico * Netherlands * Poland * Romania * Russian Federation * Slovakia * South Africa * Spain * Ukraine * United Kingdom * United States
Interventions
DRUGK-877
0.2mg tablet
DRUGPlacebo
K-877 matching placebo tablet
Sponsors
Brigham and Women's Hospital
Kowa Research Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Fasting TG ≥ 200 mg/dL (2.26 mmol/L) and \< 500 mg/dL (5.65 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest) 2. HDL-C ≤ 40 mg/dL (1.03 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest) 3. Type 2 diabetes of longer than 12 weeks duration documented in medical records, for example: local laboratory evidence through medical record review of elevated HbA1c (≥ 6.5% \[48 mmol/mol\]), elevated plasma glucose (fasting ≥ 126 mg/dL \[7.0 mmol/L\], 2-hour ≥ 200 mg/dL \[11.1 mmol/L\] during oral glucose tolerance testing, or random value ≥ 200 mg/dL with classic symptoms, or currently taking medication for treatment of diabetes; AND either 1. Age ≥ 50 years if male or ≥ 55 years if female (primary prevention cohort); OR 2. Age ≥ 18 years and established systemic atherosclerosis (secondary prevention cohort), defined as any 1 of the following: * i. Prior MI or ischemic (non-hemorrhagic) stroke * ii. Coronary angiographic lesion of ≥ 60% stenosis in a major epicardial vessel or ≥ 50% left main stenosis * iii. Asymptomatic carotid disease with ≥ 70% carotid artery stenosis * iv. Symptomatic carotid disease with ≥ 50% carotid artery stenosis * v. Symptomatic lower extremity PAD (ie, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle-brachial index ≤ 0.9 or other diagnostic testing \[eg, toe-brachial index, angiogram, or other imaging study\]) * vi. Prior arterial revascularization procedure (including coronary, carotid, or peripheral angioplasty/stenting, bypass, or atherectomy/endarterectomy)
Exclusion criteria
1. Current or planned use of fibrates or agents with PPAR-α agonist activity (eg, saroglitazar) within 6 weeks (42 days) of Visit 1 (Screening/Enrollment Visit). Note: PPAR-γ agonists (eg, glizatones such as pioglitazone and rosiglitazone) are allowed 2. Known sensitivity to PPAR-α agonists or tablet excipients 3. Initiation of, or change in, current TG-lowering therapy within 12 weeks of Visit 1 (if applicable). Note: TG-lowering therapy is defined as niacin \> 100 mg/day or dietary supplements or prescription omega-3 fatty acids \> 1 g/day 4. Type 1 diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of 4-component Composite Primary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Coronary Revascularization, or CV Death) | From Baseline to a Median of 3.3 Years | Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint, which includes nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, or cardiovascular (CV) death. Each participant is counted only once, regardless of any subsequent events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of the 3-component Composite Endpoint (Nonfatal Myocardial Infarction, Nonfatal Ischemic Stroke, or Cardiovascular Death) | From Baseline to a Median of 3.3 Years | Number of Participants with First Occurrence of Composite Cardiovascular Events (nonfatal myocardial infarction, nonfatal ischemic stroke, or cardiovascular death) |
| Number of Participants With First Occurrence of Any Component of the Primary Endpoint or Hospitalization for Heart Failure | From Baseline to a Median of 3.3 Years | Event is the first occurrence of any component of the composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, cardiovascular death, or hospitalization for heart failure |
| Number of Participants With Occurrence of Any Component of the Primary Endpoint or All-Cause Mortality | From Baseline to a Median of 3.3 Years | Event is the first occurrence of any component of the composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, cardiovascular death, or all-cause mortality. |
| Total Number of Events of the 4-component Composite Primary Endpoint | From Baseline to a Median of 3.3 Years | Total number of events for the 4-component composite primary endpoint, counting all occurrences, including multiple events in the same participant. The endpoint events include nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, and cardiovascular (CV) death. |
| Number of Participants With First Occurrence of Any New or Worsening Peripheral Artery Disease (PAD) | From Baseline to a Median of 3.3 Years | Any new or worsening Peripheral artery disease (PAD), defined as incidence of lower extremity revascularization, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle-brachial index ≤ 0.9 or other diagnostic testing (eg, toe-brachial index, angiogram, or other imaging study) |
| Number of Participants With First Occurrence of Nonfatal Myocardial Infarction | From Baseline to a Median of 3.3 Years | — |
| Number of Participants With First Occurrence of Nonfatal Ischemic Stroke | From Baseline to a Median of 3.3 Years | — |
| Number of Participants With First Occurrence of Coronary Revascularization | From Baseline to a Median of 3.3 Years | — |
| Number of Participants With First Occurrence of Cardiovascular Death | From Baseline to a Median of 3.3 Years | — |
| Number of Participants With First Occurrence of the 4-component Composite Secondary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Hospitalization for Unstable Angina Requiring Unplanned Coronary Revascularization, or CV Death) | From Baseline to a Median of 3.3 Years | The 4-component composite secondary endpoints events are nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization, or cardiovascular death |
| Percent Change From Baseline to Month 4 for Total Cholesterol (TC) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Fasting Triglycerides | Baseline to 4 Months | — |
| Percent Change From Baseline to Month 4 for HDL - Cholesterol (HDL-C) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Calculated Non-HDL Cholesterol (Non-HDL-C) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Calculated VLDL Cholesterol | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Apolipoprotein A1 (ApoA1) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Apolipoprotein CIII (ApoC3) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 4 for Apolipoprotein E (ApoE) | Baseline to Month 4 | — |
| Percent Change From Baseline to Month 6 for Non-fasting Remnant Cholesterol | Baseline to Month 6 | — |
| Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | From Baseline to a Median of 3.3 Years | Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death), reported as a subgroup analysis by PPAR-α gene variants (TT, CT, CC). |
Countries
Argentina, Brazil, Bulgaria, Canada, Colombia, Czechia, Denmark, France, Germany, Hungary, India, Israel, Japan, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russia, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Prior to treatment, participants attended a Prescreening Visit, a Screening/Enrollment Visit and a Placebo Run-In Period. Eligible subjects who were compliant with study treatment during the Placebo Run-In Period returned for the Randomization Visit, at which time they were randomly allocated to receive either pemafibrate or a matching placebo tablet.
Participants by arm
| Arm | Count |
|---|---|
| Pemafibrate Participants receiving K-877 tablets administered twice daily. | 5,240 |
| Placebo Participants receiving Placebo matching tablet twice daily. | 5,257 |
| Total | 10,497 |
Baseline characteristics
| Characteristic | Placebo | Pemafibrate | Total |
|---|---|---|---|
| Age, Continuous | 63.56 Years STANDARD_DEVIATION 8.411 | 63.28 Years STANDARD_DEVIATION 8.524 | 63.42 Years STANDARD_DEVIATION 8.468 |
| Cardiovascular Diseases and Risk Factors at Baseline Established CV Disease No | 1713 Participants | 1695 Participants | 3408 Participants |
| Cardiovascular Diseases and Risk Factors at Baseline Established CV Disease Yes | 3544 Participants | 3545 Participants | 7089 Participants |
| Cardiovascular Diseases and Risk Factors at Baseline Statin Status No | 219 Participants | 220 Participants | 439 Participants |
| Cardiovascular Diseases and Risk Factors at Baseline Statin Status Yes | 5038 Participants | 5020 Participants | 10058 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1007 Participants | 1014 Participants | 2021 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4213 Participants | 4187 Participants | 8400 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 37 Participants | 39 Participants | 76 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 76 Participants | 73 Participants | 149 Participants |
| Race/Ethnicity, Customized Asian Indian | 80 Participants | 97 Participants | 177 Participants |
| Race/Ethnicity, Customized Bangladeshi | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 136 Participants | 134 Participants | 270 Participants |
| Race/Ethnicity, Customized Chinese | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Declined | 12 Participants | 20 Participants | 32 Participants |
| Race/Ethnicity, Customized Filipino | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Guamanian or Chamorro | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Japanese | 146 Participants | 162 Participants | 308 Participants |
| Race/Ethnicity, Customized Korean | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiracial | 32 Participants | 29 Participants | 61 Participants |
| Race/Ethnicity, Customized Native Hawaiian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 201 Participants | 208 Participants | 409 Participants |
| Race/Ethnicity, Customized Other Asian | 10 Participants | 13 Participants | 23 Participants |
| Race/Ethnicity, Customized Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Pakistani | 6 Participants | 13 Participants | 19 Participants |
| Race/Ethnicity, Customized Samoan | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Vietnamese | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4549 Participants | 4484 Participants | 9033 Participants |
| Sex: Female, Male Female | 1448 Participants | 1443 Participants | 2891 Participants |
| Sex: Female, Male Male | 3809 Participants | 3797 Participants | 7606 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 308 / 5,264 | 310 / 5,274 |
| other Total, other adverse events | 2,817 / 5,264 | 2,883 / 5,274 |
| serious Total, serious adverse events | 1,715 / 5,264 | 1,663 / 5,274 |
Outcome results
Primary
Number of Participants With First Occurrence of 4-component Composite Primary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Coronary Revascularization, or CV Death)
Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint, which includes nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, or cardiovascular (CV) death. Each participant is counted only once, regardless of any subsequent events.
Time frame: From Baseline to a Median of 3.3 Years
Population: Intention to treat population (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of 4-component Composite Primary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Coronary Revascularization, or CV Death) | 590 participants |
| Placebo | Number of Participants With First Occurrence of 4-component Composite Primary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Coronary Revascularization, or CV Death) | 570 participants |
95% CI: [0.92, 1.16]
Secondary
Number of Participants With First Occurrence of Any Component of the Primary Endpoint or Hospitalization for Heart Failure
Event is the first occurrence of any component of the composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, cardiovascular death, or hospitalization for heart failure
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Any Component of the Primary Endpoint or Hospitalization for Heart Failure | 670 participants |
| Placebo | Number of Participants With First Occurrence of Any Component of the Primary Endpoint or Hospitalization for Heart Failure | 645 participants |
95% CI: [0.93, 1.16]
Secondary
Number of Participants With First Occurrence of Any New or Worsening Peripheral Artery Disease (PAD)
Any new or worsening Peripheral artery disease (PAD), defined as incidence of lower extremity revascularization, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle-brachial index ≤ 0.9 or other diagnostic testing (eg, toe-brachial index, angiogram, or other imaging study)
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Any New or Worsening Peripheral Artery Disease (PAD) | 138 participants |
| Placebo | Number of Participants With First Occurrence of Any New or Worsening Peripheral Artery Disease (PAD) | 159 participants |
95% CI: [0.69, 1.09]
Secondary
Number of Participants With First Occurrence of Cardiovascular Death
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Cardiovascular Death | 145 participants |
| Placebo | Number of Participants With First Occurrence of Cardiovascular Death | 139 participants |
95% CI: [0.83, 1.32]
Secondary
Number of Participants With First Occurrence of Coronary Revascularization
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Coronary Revascularization | 340 participants |
| Placebo | Number of Participants With First Occurrence of Coronary Revascularization | 347 participants |
95% CI: [0.84, 1.14]
Secondary
Number of Participants With First Occurrence of Nonfatal Ischemic Stroke
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Nonfatal Ischemic Stroke | 96 participants |
| Placebo | Number of Participants With First Occurrence of Nonfatal Ischemic Stroke | 106 participants |
95% CI: [0.69, 1.19]
Secondary
Number of Participants With First Occurrence of Nonfatal Myocardial Infarction
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of Nonfatal Myocardial Infarction | 210 participants |
| Placebo | Number of Participants With First Occurrence of Nonfatal Myocardial Infarction | 182 participants |
95% CI: [0.95, 1.41]
Secondary
Number of Participants With First Occurrence of the 3-component Composite Endpoint (Nonfatal Myocardial Infarction, Nonfatal Ischemic Stroke, or Cardiovascular Death)
Number of Participants with First Occurrence of Composite Cardiovascular Events (nonfatal myocardial infarction, nonfatal ischemic stroke, or cardiovascular death)
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of the 3-component Composite Endpoint (Nonfatal Myocardial Infarction, Nonfatal Ischemic Stroke, or Cardiovascular Death) | 396 participants |
| Placebo | Number of Participants With First Occurrence of the 3-component Composite Endpoint (Nonfatal Myocardial Infarction, Nonfatal Ischemic Stroke, or Cardiovascular Death) | 386 participants |
95% CI: [0.89, 1.18]
Secondary
Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC)
Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death), reported as a subgroup analysis by PPAR-α gene variants (TT, CT, CC).
Time frame: From Baseline to a Median of 3.3 Years
Population: This analysis includes participants from the intent-to-treat population who consented to genetic testing for the PPAR-α gene. Participants who did not provide consent for genetic testing are excluded from the numbers reported for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | TT variant | 114 Count of Participants |
| Pemafibrate | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | CT variant | 177 Count of Participants |
| Pemafibrate | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | CC variant | 63 Count of Participants |
| Placebo | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | TT variant | 117 Count of Participants |
| Placebo | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | CT variant | 156 Count of Participants |
| Placebo | Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC) | CC variant | 65 Count of Participants |
Comparison: TT Variant95% CI: [0.75, 1.26]
Comparison: CT Variant95% CI: [0.96, 1.47]
Comparison: CC Variant95% CI: [0.69, 1.39]
Secondary
Number of Participants With First Occurrence of the 4-component Composite Secondary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Hospitalization for Unstable Angina Requiring Unplanned Coronary Revascularization, or CV Death)
The 4-component composite secondary endpoints events are nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization, or cardiovascular death
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With First Occurrence of the 4-component Composite Secondary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Hospitalization for Unstable Angina Requiring Unplanned Coronary Revascularization, or CV Death) | 447 participants |
| Placebo | Number of Participants With First Occurrence of the 4-component Composite Secondary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Hospitalization for Unstable Angina Requiring Unplanned Coronary Revascularization, or CV Death) | 427 participants |
95% CI: [0.92, 1.2]
Secondary
Number of Participants With Occurrence of Any Component of the Primary Endpoint or All-Cause Mortality
Event is the first occurrence of any component of the composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, cardiovascular death, or all-cause mortality.
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Number of Participants With Occurrence of Any Component of the Primary Endpoint or All-Cause Mortality | 830 participants |
| Placebo | Number of Participants With Occurrence of Any Component of the Primary Endpoint or All-Cause Mortality | 806 participants |
95% CI: [0.93, 1.13]
Secondary
Percent Change From Baseline to Month 4 for Apolipoprotein A1 (ApoA1)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Apolipoprotein A1 (ApoA1) | 4.878 Percent Change | Standard Deviation 19.3749 |
| Placebo | Percent Change From Baseline to Month 4 for Apolipoprotein A1 (ApoA1) | 3.956 Percent Change | Standard Deviation 18.5293 |
p-value: 0.09178ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Apolipoprotein CIII (ApoC3)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Apolipoprotein CIII (ApoC3) | -23.397 Percent Change | Standard Deviation 31.5756 |
| Placebo | Percent Change From Baseline to Month 4 for Apolipoprotein CIII (ApoC3) | 4.861 Percent Change | Standard Deviation 56.0921 |
p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Apolipoprotein E (ApoE)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Apolipoprotein E (ApoE) | -6.5201 Percent Change | Standard Deviation 30.89475 |
| Placebo | Percent Change From Baseline to Month 4 for Apolipoprotein E (ApoE) | -0.5209 Percent Change | Standard Deviation 31.79989 |
p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Calculated Non-HDL Cholesterol (Non-HDL-C)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Calculated Non-HDL Cholesterol (Non-HDL-C) | 5.219 Percent Change | Standard Deviation 31.9262 |
| Placebo | Percent Change From Baseline to Month 4 for Calculated Non-HDL Cholesterol (Non-HDL-C) | 5.502 Percent Change | Standard Deviation 31.9739 |
p-value: 0.96689ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Calculated VLDL Cholesterol
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Calculated VLDL Cholesterol | -22.788 Percent Change | Standard Deviation 32.5741 |
| Placebo | Percent Change From Baseline to Month 4 for Calculated VLDL Cholesterol | -1.601 Percent Change | Standard Deviation 36.4352 |
p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Fasting Triglycerides
Time frame: Baseline to 4 Months
Population: * ITT Population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Fasting Triglycerides | -23.860 Percent Change | Standard Deviation 49.2289 |
| Placebo | Percent Change From Baseline to Month 4 for Fasting Triglycerides | 2.593 Percent Change | Standard Deviation 60.6399 |
p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline to Month 4 for HDL - Cholesterol (HDL-C)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for HDL - Cholesterol (HDL-C) | 10.856 Percent Change | Standard Deviation 24.7407 |
| Placebo | Percent Change From Baseline to Month 4 for HDL - Cholesterol (HDL-C) | 6.004 Percent Change | Standard Deviation 21.7838 |
p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline to Month 4 for Total Cholesterol (TC)
Time frame: Baseline to Month 4
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 4 for Total Cholesterol (TC) | 5.235 Percent Change | Standard Deviation 23.7683 |
| Placebo | Percent Change From Baseline to Month 4 for Total Cholesterol (TC) | 4.562 Percent Change | Standard Deviation 23.9991 |
p-value: 0.13496ANCOVA
Secondary
Percent Change From Baseline to Month 6 for Non-fasting Remnant Cholesterol
Time frame: Baseline to Month 6
Population: * ITT population~* The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~ * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, refusal or inability to draw blood, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pemafibrate | Percent Change From Baseline to Month 6 for Non-fasting Remnant Cholesterol | -21.27 Percent Change | Standard Deviation 46.506 |
| Placebo | Percent Change From Baseline to Month 6 for Non-fasting Remnant Cholesterol | 10.60 Percent Change | Standard Deviation 54.029 |
p-value: <0.001ANCOVA
Secondary
Total Number of Events of the 4-component Composite Primary Endpoint
Total number of events for the 4-component composite primary endpoint, counting all occurrences, including multiple events in the same participant. The endpoint events include nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, and cardiovascular (CV) death.
Time frame: From Baseline to a Median of 3.3 Years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemafibrate | Total Number of Events of the 4-component Composite Primary Endpoint | 895 Events |
| Placebo | Total Number of Events of the 4-component Composite Primary Endpoint | 892 Events |
95% CI: [0.87, 1.13]