- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03531905
Bempedoic Acid + Ezetimibe Fixed-Dose Combination (FDC) Study in Patients With Type 2 Diabetes and Elevated LDL-C
April 8, 2020 updated by: Esperion Therapeutics, Inc.
A Randomized Study to Evaluate the Efficacy and Safety of Bempedoic Acid 180 + Ezetimibe 10 Fixed-Dose Combination Compared to Ezetimibe and Placebo In Subjects With T2DM and Elevated LDL-Cholesterol
12 week study to assess the LDL-C lowering efficacy, other lipid and glycemic measures, and safety of bempedoic acid/ezetimibe FDC compared to ezetimibe and placebo in patients with type 2 diabetes (T2D) and elevated LDL-C
Study Overview
Status
Completed
Conditions
Detailed Description
Assess efficacy of FDC vs. ezetimibe vs. placebo for 12 week LDL-C lowering, changes in atherogenic lipids, hsCRP and exploratory glycemic measures as well as safety in patients with type 2 diabetes and elevated LDL-C.
Study Type
Interventional
Enrollment (Actual)
242
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Lincoln, California, United States, 95648
- Clinical Trials Research
-
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Florida
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Miami, Florida, United States, 33126
- Finlay Medical Research
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Kentucky
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Louisville, Kentucky, United States, 40213
- L-MARC Research Center
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Virginia
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Suffolk, Virginia, United States, 23435
- Hampton Roads Center for Clinical Research
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Type 2 diabetes for 6 months or greater
- Currently taking stable diabetes medication for 3 months or greater
- HbA1c between 7-10%
- LDL-cholesterol greater than 70 mg/dL
- Women must not be pregnant, lactating, or planning to become pregnant within 30 days after last dose of study medication; and must be postmenopausal, surgically sterile, or willing to use 1 acceptable form of birth control during the study through 30 days after the last dose of study medication
Exclusion Criteria:
- Body mass index > 40 kg/m2
- History of documented clinically significant cardiovascular disease
- Fasting triglycerides > 400 mg/dL
- History of Type 1 diabetes
- Uncontrolled hypothyroidism, liver dysfunction, renal dysfunction, gastrointestinal condition that may affect drug absorption, hematologic or coagulation disorder or active malignancy
- History of drug or alcohol abuse within 2 years
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bempedoic acid + Ezetimibe FDC
Bempedoic acid + Ezetimibe FDC Oral Tablet; Placebo oral capsule
|
Experimental therapy of bempedoic acid 180 mg + ezetimibe 10 mg FDC tablet
Placebo over-encapsulated for blinding purposes
|
Active Comparator: Ezetimibe 10 mg
Ezetimibe 10Mg Oral Tablet; Placebo Oral Tablet
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Ezetimibe 10 mg tablet, overencapsulated for blinding purposes
Other Names:
Placebo tablet, matched for the FDC product for blinding purposes
|
Placebo Comparator: Placebo
Placebo Oral Tablet, Placebo oral capsule
|
Placebo over-encapsulated for blinding purposes
Placebo tablet, matched for the FDC product for blinding purposes
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12/End of Study (EOS) in Low-density Lipoprotein Cholesterol (LDL-C)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for LDL-C.
Baseline was defined as the average of LDL-C values at the Screening Visit 3 (Visit S3) and the Treatment Visit 1 (Visit T1) (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for LDL-C was imputed using the last observation carried forward (LOCF) method.
Percent change from Baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For LDL-C, if a measured LDL-C value was available, measured LDL-C was used.
|
Baseline; Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12/EOS in LDL-C (Comparing Ezetimibe With Placebo)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for LDL-C.
Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for LDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for LDL-C was imputed using the LOCF method.
Percent change from Baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For LDL-C, if a measured LDL-C value was available, measured LDL-C was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for hsCRP.
Baseline was defined as the last value prior to the first dose of investigational medicinal product (IMP).
Percent change from Baseline for hsCRP was analyzed using a non-parametric approach.
Percent change from Baseline was calculated as: ([hsCRP value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For hsCRP, if a measured hsCRP value was available, measured hsCRP was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for non-HDL-C.
Baseline was defined as the average of non-HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for non-HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for non-HDL-C was imputed using the LOCF method.
Percent change from Baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For non-HDL-C, if a measured non-HDL-C value was available, measured non-HDL-C was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for TC.
Baseline was defined as the average of TC values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for TC was imputed using the LOCF method.
Percent change from Baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For TC, if a measured TC value was available, measured TC was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for apo B. Baseline was defined as the last value prior to the first dose of IMP.
Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for apo B was imputed using the LOCF method.
Percent change from Baseline was calculated as: ([apo B value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For apo B, if a measured apo B value was available, measured apo B was used.
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Baseline; Week 12
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Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for TGs.
Baseline was defined as the average of TG values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for TGs was analyzed using a non-parametric approach.
Percent change from Baseline was calculated as: ([TG value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For TGs, if a measured TG value was available, measured TG was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for HDL-C.
Baseline was defined as the average of HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
Percent change from Baseline for HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate.
Missing data for HDL-C was imputed using the LOCF method.
Percent change from Baseline was calculated as: ([HDL-C value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For HDL-C, if a measured HDL-C value was available, measured HDL-C was used.
|
Baseline; Week 12
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Number of Participants With LDL-C <70 Milligrams Per Deciliter (mg/dL) at Week 12
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for LDL-C.
For LDL-C, if a measured LDL-C value was available, measured LDL-C was used.
|
Week 12
|
Secondary Outcome Measure: Number of Participants With an LDL-C Reduction of ≥50% From Baseline at Week 12
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for LDL-C.
Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1).
If only 1 value was available, the single value was used as Baseline.
LDL-C reduction from Baseline was calculated as the LDL-C value at Week 12 minus the Baseline value.
For LDL-C, if a measured LDL-C value was available, measured LDL-C was used.
|
Baseline; Week 12
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Change From Baseline to Week 12 in Hemoglobin A1C (HbA1c)
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for HbA1c.
Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1).
Change from Baseline was calculated as the HbA1c value at Week 12 minus the Baseline value.
For HbA1c, if a measured HbA1c value was available, measured HbA1c was used.
|
Baseline; Week 12
|
Percent Change From Baseline to Week 12 in HbA1c
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for HbA1c.
Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1).
Percent change from Baseline for HbA1C was analyzed using ANCOVA, with treatment as factor and Baseline HbA1C value as a covariate.
Percent change from Baseline for HbA1c was calculated as: ([HbA1c value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For HbA1c, if a measured HbA1c value was available, measured HbA1c was used.
|
Baseline; Week 12
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12 in Fasting Plasma Glucose
Time Frame: Baseline; Week 12
|
Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals.
Samples were collected and analyzed for fasting plasma glucose.
Baseline was defined as the last value prior to the first dose of study drug (on or before T1).
Percent change from Baseline for fasting plasma glucose was analyzed using ANCOVA, with treatment as factor and Baseline fasting plasma glucose as a covariate.
Percent change from Baseline for fasting plasma glucose was calculated as: ([fasting plasma glucose value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For fasting plasma glucose, if a measured fasting plasma glucose value was available, measured fasting plasma glucose was used.
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Baseline; Week 12
|
Percent Change From Baseline to Week 12 in 2-hour Post Prandial Plasma Glucose (PPG)
Time Frame: Baseline; Week 12
|
Blood samples were drawn 2 hours ± 5 minutes after the start of the meal.
Samples were collected and analyzed for PPG.
Baseline was defined as the last value prior to the first dose of study drug (on or before T1).
Percent change from Baseline for PPG was calculated as: ([PPG value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
For PPG, if a measured PPG value was available, measured PPG was used.
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Baseline; Week 12
|
Percent Change From Baseline to Week 12 in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Index
Time Frame: Baseline; Week 12
|
The HOMA-IR index was calculated from the fasting glucose and insulin values that were obtained at each clinic visit (Day 1/Visit T1, Week 4/Visit T2, and Week 12/Visit T3) during the double-blind treatment period, using the formula: (fasting glucose [millimoles per milliliter {mmol/ml}] x fasting insulin [micro International Units per milliliter {μIU/ml}]) divided by 22.5.
Percent change from Baseline for HOMA-IR index was analyzed using ANCOVA, with treatment as factor and Baseline HOMA-IR index as a covariate.
Baseline was defined as the last value prior to the first dose of study drug (on or before T1).
Percent change from Baseline for HOMA-IR index was calculated as: ([HOMA-IR index value at Week 12 minus Baseline value] divided by [Baseline value]) multiplied by 100.
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Baseline; Week 12
|
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Time Frame: up to approximately 16 weeks
|
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind IMP through 30 days after the last dose of double-blind IMP.
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, including control, and which does not necessarily have a causal relationship with treatment.
An AE is: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (e.g., electrocardiogram or x-ray) that results in symptoms, a change in treatment, or discontinuation from IMP; or an adverse drug reaction.
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up to approximately 16 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 9, 2018
Primary Completion (Actual)
June 18, 2019
Study Completion (Actual)
June 18, 2019
Study Registration Dates
First Submitted
May 9, 2018
First Submitted That Met QC Criteria
May 9, 2018
First Posted (Actual)
May 22, 2018
Study Record Updates
Last Update Posted (Actual)
April 9, 2020
Last Update Submitted That Met QC Criteria
April 8, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Ezetimibe
- 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Other Study ID Numbers
- 1002FDC-058
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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