Assessment of the Long-Term Safety and Efficacy of Bempedoic Acid (CLEAR Harmony OLE)

A Multicenter Open-Label Extension (OLE) Study To Assess The Long-Term Safety and Efficacy of Bempedoic Acid (ETC-1002) 180 MG

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03067441

Enrollment

1462

Registered

2017-03-01

Start date

2017-02-03

Completion date

2019-11-05

Last updated

2021-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atherosclerotic Cardiovascular Disease, Hypercholesterolemia

Keywords

hyperlipidemia, cholesterol, heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease, ASCVD, HeFH, LDL

Brief summary

The purpose of this study is to see if bempedoic acid (ETC-1002) is safe and well-tolerated in patients with high cardiovascular risk and elevated LDL cholesterol that is not adequately controlled by their current therapy.

Interventions

DRUGbempedoic acid

bempedoic acid 180 mg tablets taken orally, once per day.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Successfully completed CLEAR Harmony (1002-040) parent study

Exclusion criteria

* Experienced a treatment-related SAE that led to study drug discontinuation in the CLEAR Harmony (1002-040) parent study. * Medical condition requires lipid measurement and/or adjustment of background lipid-regulating therapy.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Up to Week 82	TEAEs are defined as adverse events that began or worsened in severity after the first dose of investigational medicinal product (IMP) until 30 days after the last dose in the Open-Label Extension (OLE) Study.

Secondary

Measure	Time frame	Description
Mean Change From Parent Study Baseline in LDL-C at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Mean change from Baseline was calculated as: Mean LDL-C value at Week 52/Week 78 minus Mean Parent Study Baseline value. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 52 and 78	Baseline; Week 52 and Week 72	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: non-HDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in Total Cholesterol at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Total cholesterol value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in Apolipoprotein B (ApoB) at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: ApoB value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: hs-CRP value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in Triglycerides at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Triglycerides value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: HDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Percent Change From Parent Study Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: LDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
Mean Change From OLE Baseline in LDL-C at Weeks 52 and 78	Baseline; Week 52 and Week 72	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Mean change from Baseline was calculated as: Mean LDL-C value at Week 52/Week 78 minus Mean OLE Study Baseline value. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline in Non-HDL-C at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: non-HDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline in Total Cholesterol at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Total Cholesterol value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline ApoB at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: ApoB value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline in Hs-CRP at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: hs-CRP value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline in Triglycerides at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Triglycerides value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From OLE Baseline in HDL-C at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: HDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
Percent Change From Open-Label Extension (OLE) Study Baseline in LDL-C at Weeks 52 and 78	Baseline; Week 52 and Week 78	Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: LDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.

Countries

United States

Participant flow

Pre-assignment details

After successfully completing 52 weeks of treatment in the parent study, Study 1002-040 (NCT02666664), and meeting entry criteria, participants could enrol into this Open-label Extension (OLE) study.

Participants by arm

Arm	Count
Placebo; Bempedoic Acid In the parent study (Study 1002-040), participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies), including a maximally tolerated statin, throughout the study. Participants received open-label bempedoic acid 180 milligrams (mg) once daily by mouth for up to 78 weeks after rolling over from the parent study, followed by a 4-week period off of investigational medicinal product (IMP).	492
Bempedoic Acid; Bempedoic Acid In the parent study, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies), including a maximally tolerated statin, throughout the study. Participants received open-label bempedoic acid 180 mg once daily by mouth for up to 78 weeks after rolling over from the parent study, followed by a 4-week period off of IMP.	970
Total	1,462

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	7	14
Overall Study	Lost to Follow-up	7	5
Overall Study	Other	1	1
Overall Study	Physician Decision	1	3
Overall Study	Study Terminated by Sponsor or Investigator	1	0
Overall Study	Withdrawal by Subject	16	34

Baseline characteristics

Characteristic	Total	Bempedoic Acid; Bempedoic Acid	Placebo; Bempedoic Acid
Age, Continuous	66.9 years STANDARD_DEVIATION 8.73	66.5 years STANDARD_DEVIATION 8.81	67.5 years STANDARD_DEVIATION 8.54
Apolipoprotein B: OLE Study	82.8 mg/dL STANDARD_DEVIATION 22.07	80.4 mg/dL STANDARD_DEVIATION 21.31	87.6 mg/dL STANDARD_DEVIATION 22.74
Apolipoprotein B: Parent Study	87.2 mg/dL STANDARD_DEVIATION 20.97	88.2 mg/dL STANDARD_DEVIATION 21.71	85.1 mg/dL STANDARD_DEVIATION 19.25
HDL-C: OLE Study	47.1 mg/dL STANDARD_DEVIATION 12.66	46.1 mg/dL STANDARD_DEVIATION 13	49.0 mg/dL STANDARD_DEVIATION 11.72
High-density lipoprotein cholesterol (HDL-C): Parent Study	48.86 mg/dL STANDARD_DEVIATION 11.593	48.82 mg/dL STANDARD_DEVIATION 11.79	48.93 mg/dL STANDARD_DEVIATION 11.206
High-sensitivity C-reactive protein (hs-CRP): Parent Study	1.510 milligrams per Liter (mg/L)	1.500 milligrams per Liter (mg/L)	1.515 milligrams per Liter (mg/L)
hs-CRP: OLE Study	1.325 mg/L	1.250 mg/L	1.560 mg/L
LDL-C: OLE Study	91.0 mg/dL STANDARD_DEVIATION 30.26	86.6 mg/dL STANDARD_DEVIATION 30.18	99.5 mg/dL STANDARD_DEVIATION 28.59
Low-density lipoprotein cholesterol (LDL-C): Parent Study	101.60 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 28.156	102.94 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 29.899	98.96 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.171
N-HDL-C: OLE Study	117.9 mg/dL STANDARD_DEVIATION 34.42	113.7 mg/dL STANDARD_DEVIATION 34.57	126.1 mg/dL STANDARD_DEVIATION 32.61
Non-high-density lipoprotein cholesterol (N-HDL-C): Parent Study	128.85 mg/dL STANDARD_DEVIATION 32.809	130.09 mg/dL STANDARD_DEVIATION 34.727	126.41 mg/dL STANDARD_DEVIATION 28.531
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Asian	14 Participants	9 Participants	5 Participants
Race (NIH/OMB) Black or African American	29 Participants	23 Participants	6 Participants
Race (NIH/OMB) More than one race	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants	3 Participants	1 Participants
Race (NIH/OMB) White	1411 Participants	931 Participants	480 Participants
Sex: Female, Male Female	381 Participants	239 Participants	142 Participants
Sex: Female, Male Male	1081 Participants	731 Participants	350 Participants
Total cholesterol: OLE Study	165.0 mg/dL STANDARD_DEVIATION 36.41	159.8 mg/dL STANDARD_DEVIATION 36.41	175.2 mg/dL STANDARD_DEVIATION 34.23
Total cholesterol: Parent Study	177.73 mg/dL STANDARD_DEVIATION 34.179	178.94 mg/dL STANDARD_DEVIATION 36.057	175.33 mg/dL STANDARD_DEVIATION 30.026
Triglycerides: OLE Study	120.0 mg/dL	121.0 mg/dL	120.0 mg/dL
Triglycerides: Parent Study	124.00 mg/dL	125.00 mg/dL	122.00 mg/dL

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	3 / 492	10 / 970	13 / 1,462
other Total, other adverse events	108 / 492	201 / 970	309 / 1,462
serious Total, serious adverse events	97 / 492	202 / 970	299 / 1,462

Outcome results

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs are defined as adverse events that began or worsened in severity after the first dose of investigational medicinal product (IMP) until 30 days after the last dose in the Open-Label Extension (OLE) Study.

Time frame: Up to Week 82

Population: Safety Population: all enrolled participants who received at least 1 dose of bempedoic acid in the OLE Study

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with serious TEAEs	97 Participants
Placebo; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of moderate severity	211 Participants
Placebo; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs	385 Participants
Placebo; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of mild severity	93 Participants
Placebo; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of severe severity	81 Participants
Bempedoic Acid; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of mild severity	195 Participants
Bempedoic Acid; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of moderate severity	403 Participants
Bempedoic Acid; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of severe severity	160 Participants
Bempedoic Acid; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with serious TEAEs	202 Participants
Bempedoic Acid; Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs	758 Participants
OLE Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of severe severity	241 Participants
OLE Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs	1143 Participants
OLE Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with serious TEAEs	299 Participants
OLE Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of mild severity	288 Participants
OLE Bempedoic Acid	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Participants with TEAEs of moderate severity	614 Participants

Secondary

Mean Change From OLE Baseline in LDL-C at Weeks 52 and 78

Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Mean change from Baseline was calculated as: Mean LDL-C value at Week 52/Week 78 minus Mean OLE Study Baseline value. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.

Time frame: Baseline; Week 52 and Week 72