Primary:* To characterize the safety and tolerability of long-term administration of bempedoic acid (ETC-1002) 180 mgSecondary:* To characterize the efficacy of long-term administration of bempedoic acid 180 mg/day as assessed by changes in low-…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Patient incidence of adverse events (AEs)
Secondary outcome
* Percent change from baseline in LDL-C at Weeks 52 and 78
* Change from baseline in LDL-C at Weeks 52 and 78
* Percent change from baseline in non-HDL-C at Weeks 52 and 78
* Percent change from baseline in TC at Weeks 52 and 78
* Percent change from baseline in ApoB at Weeks 52 and 78
* Percent change from baseline in hs-CRP at Weeks 52 and 78
* Percent change from baseline in TG at Weeks 52 and 78
* Percent change from baseline in HDL-C at Weeks 52 and 78
Background summary
Bempedoic acid is a first-in-class small molecule inhibitor of ACL, an enzyme
upstream of HMG-CoA in the cholesterol biosynthesis pathway. Bempedoic acid is
a prodrug that requires activation in liver to ETC-1002-co-enzyme A
(ETC-1002-CoA), which mediates competitive inhibition of ACL. Inhibition of ACL
by ETC-1002-CoA decreases cholesterol synthesis in liver leading to increased
LDLR expression and LDL particle clearance from the blood. Therefore,
inhibition of ACL by ETC-1002-CoA reduces LDL-C via the same pathway as HMG-CoA
reductase inhibition by statins.
Bempedoic acid has been evaluated in 21 completed clinical studies, with over
1000 subjects/patients receiving bempedoic acid doses from 2.5 mg/day up to 240
mg/day (multiple doses). All multiple-dose studies have demonstrated
consistent, clinically meaningful LDL-C lowering with bempedoic acid treatment
and have shown a positive safety profile.
This is a multicenter open-label extension (OLE) study designed to assess the
long-term safety and efficacy of bempedoic acid 180 mg. All patients will
receive open-label bempedoic acid 180 mg for up to 1.5 years after rolling over
from Study 1002-040 (parent study) followed by a follow-up period off study
drug for 4 weeks. The total duration in the study will be 19 months.
Bempedoic acid in this study is currently being evaluated as an add-on to
lipid-modifying therapy in high-risk CV patients (ie, those with HeFH and/or
ASCVD) who have not achieved their LDL-C goal despite maximally tolerated
lipid-modifying therapy.
The primary clinical hypothesis is that long-term exposure of bempedoic acid
(ETC-1002) 180 mg will be safe and well tolerated.
Study objective
Primary:
* To characterize the safety and tolerability of long-term administration of
bempedoic acid (ETC-1002) 180 mg
Secondary:
* To characterize the efficacy of long-term administration of bempedoic acid
180 mg/day as assessed by changes in low-density lipoprotein cholesterol
(LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density
lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol
(TC), triglycerides (TG), and high-sensitivity C-reactive protein (hs-CRP) in
patients with hyperlipidemia
Study design
This is a multicenter open-label extension study designed to assess the
long-term safety and efficacy of bempedoic acid (ETC-1002) 180 mg. All patients
will receive open-label bempedoic acid 180 mg for up to 1.5 years after rolling
over from the parent study (Study 1002-040) followed by a follow-up period off
study drug for 4 weeks. Investigators, site staff, patients, and the study team
will be masked to study lipid levels until the Week 12 study visit, after which
time lipid values will be made available to sites. While this is an open-label
study where all patients will receive active treatment with bempedoic acid,
blinding of the treatment that patients received during the parent study must
be maintained for all patients unless, in the opinion of the Investigator, the
safety of the patient may be at risk.
Patients will have visits every 3 months. Patients will be required to visit
the site at baseline (end of study [EOS] parent), Week 12, Week 52, Week 78
and Week 82. Phone visits will occur at Weeks 24, 36, and 64.
Patients who withdraw from investigational medicinal product (IMP) treatment
will be asked to continue to be followed for safety using the
protocol-specified visit schedule. For details of study assessments, see the
Schedule of Events in Appendix 1 of the protocol.
Intervention
All patients will receive open-label bempedoic acid 180 mg for up to 1.5 years
after rolling over from parent study (Study 1002-040). Bempedoic acid (180 mg)
will be ingested once daily with or without food. On clinic days patients will
come to the clinic in the fasted state and study drug will be administered
after laboratories are obtained.
Study burden and risks
To date, the nonclinical and clinical data indicate that bempedoic acid has a
favorable risk-benefit profile. The ability of bempedoic acid to achieve
clinically meaningful LDL-C-lowering responses while demonstrating a favorable
tolerability profile in a variety of patient populations supports continued
development of bempedoic acid, an oral ACL inhibitor, in Phase 3 studies.
Please refer to the most recent IB for additional information regarding
previous human experience.
3891 Ranchero Drive Suite 150
Michigan 48108 Ann Arbor
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3891 Ranchero Drive Suite 150
Michigan 48108 Ann Arbor
US
Listed location countries
Age
Inclusion criteria
Each patient must meet the following criteria to be enrolled in this study:
Successfully completed the parent study (1002-040) and meet both of the following
criteria:
* The patient was compliant with the parent study requirements including study visits,
procedures, and investigational medicinal product (IMP) in the opinion of the
principal investigator.
* The patient was able to tolerate IMP through the end of the parent study.
Exclusion criteria
1. Female patient is not willing to use at least 1 acceptable method of birth control during treatment and for an additional 30 days after the end of treatment unless patient is sterilized or postmenopausal;
a. Menopause is defined as greater than 55 years and *1 year without menses, less than 55 years and *1 year without menses with follicle-stimulating hormone (FSH) *40.0 IU/L, or surgically sterile (including hysterectomy and/or bilateral oophorectomy);
b. Acceptable methods of birth control include: oral birth control medications; placement of an intrauterine device (IUD) with or without hormones; barrier methods including condom or occlusive cap with spermicidal foam or spermicidal jelly; vasectomized male partner who is the sole partner for this patient; or true abstinence where it is the preferred and usual lifestyle of the patient (not including periodic abstinence such as calendar, ovulation, symptothermal, postovulation methods, or withdrawal).
2. Patient is pregnant or breastfeeding, or might become pregnant during treatment and/ or within 30 days after the end of treatment
3. Unreliability as a study participant based on the investigator*s (or designee*s) knowledge of the patient (eg, inability or unwillingness to adhere to the protocol) 4. Experienced a treatment-related SAE that led to study drug discontinuation in the parent study
5. Disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
6. Have any medical condition that in the opinion of the investigator may affect patient safety or ability to complete scheduled assessments
7. Patient*s medical condition requires lipid measurement and/or adjustment of background lipid-regulating therapy during the first 12 weeks of study participation
8. Known sensitivity to any of the products to be administered during dosing
9. Currently enrolled in another investigational device or drug study (excluding ETC-1002-040), or less than 30 days since ending another investigational device or drug study(s),or receiving or planning to receive other investigational agent(s) during this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004115-12-NL |
| CCMO | NL60616.100.17 |