A clinical trial study to assess the effects of Bempedoic acid on heart related events in patients with or at high risk for heart related issues who are unable to tolerate statins (class of drugs that reduce cholesterol in blood)

• Register: CTRI
• Last refreshed on: 29 April 2024
• Main ID: CTRI/2017/10/010233
• Date of registration: 27-10-2017
• Prospective Registration: Yes
• Primary sponsor: Esperion Therapeutics Inc
• Public title: A clinical trial study to assess the effects of Bempedoic acid on heart related events in patients with or at high risk for heart related issues who are unable to tolerate statins (class of drugs that reduce cholesterol in blood)
• Scientific title: A Randomized, Double-Blind, Placebo Controlled Study To Assess The Effects Of Bempedoic Acid (Etc-1002) On The Occurrence Of Major Cardiovascular Events In Patients With, Or At High Risk For, Cardiovascular Disease Who Are Statin Intolerant
• Date of first enrolment: 06-11-2017
• Target sample size: 12604
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=20808
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Chile, Colombia, Croatia, Czech Republic, Denmark, Estonia, Germany, Hungary, India, Latvia, Lithuania, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia , Slovakia, South Africa, Spain, Turkey, Ukraine, United Kingdom, United States of America

Contacts

• Name: Suneela Thatte
• Affiliation: IQVIA RDS (India) Private Ltd

• Name: Suneela Thatte
• Affiliation: IQVIA RDS (India) Private Ltd

Key inclusion & exclusion criteria

Inclusion criteria: 1.Provision of signed informed consent prior to any study-specific procedure.

2. Patient reported statin intolerance (SI) due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued resulting in an inability to tolerate:

• 2 or more statins at any dose, or

• 1 statin at any dose and unwilling to attempt a second statin or advised by a physician to not attempt a second statin.

3. Written confirmation by both patient and investigator that the patient is statin intolerant as defined above, aware of the benefit of statin use to reduce the risk of MACE including death, and also aware that many other patients who are unable to tolerate a statin are able to tolerate a different statin or dose.

4. Age =18 years or legal age of majority based on regional law, whichever is greater, and =85 years at Week -5 (Visit S1).

5.Men and nonpregnant, nonlactating women. Women must be one of the following:

a.Naturally postmenopausal defined as =1 year without menses and:

•=55 years, or

• <55 years with follicle-stimulating hormone (FSH) =40.0 IU/L, or

b.Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal ligation,

or

c.Women of childbearing potential willing to use one acceptable method of birth control during the study and for 30 days after the end of treatment including:

•oral birth control medications,

•placement of an intrauterine device 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,

•true abstinence (not including periodic abstinence such as calendar, ovulation, symptothermal, postovulation methods, or withdrawal).

There are no protocol-specific birth control requirements for men with partners who are able to become pregnant.

6. Fasting LDL-C =100 mg/dL (2.6 mmol/L) at Week -5 (Visit S1) while taking stable (4 weeks prior to Visit S1) and optimized background LDL-C-lowering therapies that may include very low dose statin (see definition above), ezetimibe, niacin, bile acid resins, fibrates, and/or proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.

Note: A single repeat of LDL-C may be completed prior to initiation of the single-blind Run–in Period. For those patients who have a repeat LDL-C, the repeat value will be used to determine eligibility.

7.History of, or at high risk for, CVD including documented evidence of one or more of the following:

a.Coronary artery disease, defined by:

•MI (either ST-elevation MI or non-ST-elevation MI) occurring greater than 90 days prior to screening, or

•Percutaneous coronary or surgical coronary revascularization, occurring greater than 90 days prior to screening, or

•Angiographic stenosis of >50% in a least 1 major coronary artery (native or graft vessel), as documented by selective coronary angiography or computed tomography angiography (CTA), or

b.Symptomatic peripheral arterial disease (PAD) , defined by:

•Peripheral vascular disease with symptoms of claudication or resting limb ischemia with either ankle brachial index <0.9 performed by a vascular lab or angiogram (including CTA) showing =50% stenosis, or

•Peripheral arterial revascularization (surgical
Exclusion criteria: Patients who meet any of the following criteria will not be eligible to participate:

1.Total fasting TG >500 mg/dL (5.6 mmol/L) at Week -5 (Visit S1).

Note: A single repeat of TG may be completed prior to initiation of the single-blind Run-in Period. For those patients who have a repeat TG, the repeat value will be used to determine eligibility.

2.Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73 m2 at Week -5 (Visit S1).

Note: A single repeat of eGFR may be completed prior to randomization. For those patients who have a repeat eGFR, the repeat value will be used to determine eligibility.

3.Forms of CVD that include any of the following:

a.Recent (within 90 days prior to screening) transient ischemic attack (TIA)

b.Recent (within 90 days of screening) unstable or symptomatic cardiac arrhythmia (including any associated medication changes). Patients with stable well-controlled atrial arrhythmias will be allowed to participate in the study.

c.Patients with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the investigator to be stable for greater than 90 days prior to screening,

d.New York Heart Association (NYHA) Functional Classification Class IV heart failure,

e.Uncontrolled hypertension, defined as mean sitting systolic blood pressure (SBP)

=180 mmHg and/or diastolic blood pressure (DBP) =110 mmHg,

f.Planned coronary revascularization (patient may rescreen 3 months post-procedure).

Note: At the discretion of the investigator, BP medications can be adjusted and/or additional assessment of BP may be completed prior to randomization, with the repeat assessment value used to determine eligibility. Alternatively, patients can be rescreened if BP status has changed.

4.HbA1C =10% at Week -5 (Visit S1).

5.Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper limit of normal (ULN) at Week -5 (Visit S1). Note: At the discretion of the investigator, thyroid replacement therapy can be adjusted and/or additional measurement of TSH may be completed prior to randomization, with the repeat TSH value used to determine eligibility.

6.Liver disease or dysfunction, including:

a. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (HCV-ABVivi) at Week -4 (Visit S2), or

b. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =2.0 × ULN at Week -5 (Visit S1).

Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be completed prior to randomization. For those patients who have a repeat ALT and/or AST, the repeat value will be used to determine eligibility. Also, if test for Hepatitis C antibody is positive, but optional reflexive test for Hepatitis C RNA is negative, patient can be enrolled.

7.Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or gastric bypass) that may affect drug absorption.

8.Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at Week -5 (Visit S1).

9.Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 ye

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: I52- Other heart disorders in diseasesclassified elsewhere Health Condition 2: null- Reduction of cardiovascular disease risk

Intervention(s)

Intervention1: Bempedoic acid: Test Product: Bempedoic acid 180 mg Dose: 1 tablet daily Mode of Administration: Oral
Control Intervention1: Matching placebo tablet (placebo) 0 mg

: Test Product: Bempedoic acid 180 mg
Dose: 1 tablet daily
Mode of Administration: Oral

Reference Product: Matching placebo tablet (placebo) 0 mg
Dose: 1 tablet daily
Mode of Administration: Oral

Primary Outcome(s)

To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of major adverse cardiovascular events (MACE) in patients with, or at high risk for, cardiovascular disease (CVD) who are statin intolerant. This will be assessed with a composite primary efficacy endpoint that includes time to first occurrence of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularizationTimepoint: Entire duration

Secondary Outcome(s)

To evaluate the effect of long-term treatment with bempedoic acid 180 mg/day versus placebo on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP)Timepoint: During entire study

To evaluate the long-term safety and tolerability of bempedoic acid 180 mg/day compared to placeboTimepoint: During entire study

To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of new-onset diabetes in the prediabetes efficacy population (patients with prediabetes at baseline)Timepoint: During entire study

To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of other clinical endpoints of CV morbidity & mortality & all-cause mortalityTimepoint: During entire study

To evaluate the 12-month efficacy of treatment with bempedoic acid 180 mg/day versus placebo on absolute change in hemoglobin A1c (HbA1C) in the inadequately controlled diabetes efficacy population (patients with diabetes & having an HbA1C of 7% or greater at baseline)Timepoint: During entire study

Secondary ID(s)

1002-043 Version 4 dated 19 December 2019

Source(s) of Monetary Support

Esperion Therapeutics, Inc. 3891 Ranchero Drive, Suite 150 Ann Arbor, MI 48108 United States of America

Secondary Sponsor(s)

Quintiles Research India Private Limited

Ethics review

Status: Approved
Approval date: 25/09/2017
Contact:

Rhythm Heart Institute Ethics Committee, Near Siddharth Bunglows,, Sama- Savli Road, Vadodara-390022, Gujarat, India

Status: Approved
Approval date: 07/12/2017
Contact:

Sushruta Hospitals Ethics Committee C/ O Sushruta Multispeciality Hospital & Research Centre Private Limited., P. B. Road, Vidyanagar, Hubli-580021, Dharwar, Karnataka, India.

Status: Approved
Approval date: 23/01/2018
Contact:

Ethics Committee Kamalnayan Bajaj Hospital, Marathawada Medical & Research Institute, Gut No.43, Satara Parisar, Bajaj Marg, Beed Bypass Road, Aurangabad-431005, Maharashtra, India

Status: Approved
Approval date: 04/07/2018
Contact:

Institutional Ethics Committee of Kovai Diabetes Speciality Centre & Hospital,No.15, Vivekananda Road, Ramnagar, Coimbatore-641009Tamilnadu, India

Status: Approved
Approval date: 23/07/2018
Contact:

Scientific Research And Ethical Review CommiteeDepa1tment of Laboratory Medicine, Batra Hospital & Medical Research Centre, I, TughlakabadInstitutional Area, Mehrauli-Badarpur Road, New Delhi-110062

Status: Approved
Approval date: 01/09/2018
Contact:

BAPS Pramukh Swami Hospital Instituational Ethics committee,BAPS Pramukh Swami Hospital, Shree Pramukh Swami mahraj marg, Adajan Cross Road, Adajan, Surat- 395009

Status: Approved
Approval date: 03/10/2018
Contact:

Department of Research 14 Floor C Wing Super Speciality building Deenanath Mangeshkar Hospital and Research Centre off Karve Road Erandawane Pune-411004, Maharashtra. India

Status: Approved
Approval date: 10/10/2018
Contact:

Eternal Heart Care Centre & Research Institute - Institutional Ethics Committee 3 A, Jagatpura Road, Near Jawahar Circle, Jaipur - 302020, Rajasthan, India

Status: Approved
Approval date: 24/10/2018
Contact:

Ethics Committee, KLE University, JNMC Campus, Nehru Nagar, Belgaum 590010, Karnataka State, India

Status: Approved
Approval date: 29/10/2018
Contact:

Meditrina Institute Ethics Committee 278, Central Bazar Road, Ramdaspeth, Nagpur-440010, Maharashtra, India

Status: Approved
Approval date: 10/11/2018
Contact:

Diacon Hospital Ethics Committee No. 359-360, 19th Main, 1st Block, Rajajinagar, Bangalore: 560 010.

Status: Approved
Approval date: 03/01/2019
Contact:

Institutional Ethics Committee of B. J. Government Medical College & Sassoon General Hospitals, Pune-411001, Maharashtra, India

Status: Approved
Approval date: 11/02/2019
Contact:

institutional Ethics Committee, Government Medical College and Hospital, Department of Medicine, Medical College Square Road, Nagpur-440003, Maharashtra, India.

Status: Approved
Approval date: 27/02/2019
Contact:

Arejas Insitutional ethics Committee AIEC Arneja Heart Institute situated at 123, Ramdaspeth, Nagpur-440010 Maharashtra India

Status: Approved
Approval date: 11/04/2019
Contact:

Ethics Committee,MAMC Loknayak Hospital, Room No 122 B.L.Taneja block MAMC,LNJP Hospital, New Delhi-110002, India

Status: Approved
Approval date: 22/05/2020
Contact:

Institutional Ethics Committee, Government Medical College, Aurangabad-431001, Maharashtra, India

Status: Approved
Approval date: 25/05/2020
Contact:

S.R.Kalla Memorial Ethical Committee for Human Research, S R Kalla Memorial Gastro & General Hospital 78-79, Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C-Scheme, Jaipur-302001 Rajasthan, India.

Status: Approved
Approval date: 31/05/2020
Contact:

KRM Hospital Ethics Commitee,KRM Hospital and Research Centre, 3/92-93, Vijayant Khand, Gomtinagar, Lucknow-226010, Uttar Pradesh

Status: Approved
Approval date: 15/06/2020
Contact:

Crescent Hospital Institutional Ethics CommitteeNear Lokmat Square, Dhantoli, Nagpur-440012

Status: Approved
Approval date: 16/06/2020
Contact:

Shri B.D. Mehta Mahavir Heart Institute Ethics Committee

Status: Approved
Approval date: 17/06/2020
Contact:

Ethics Committee, Fortis Escorts Hospital, Neelam Bata Road, Faridabad-121001, Haryana, India

Status: Approved
Approval date: 17/06/2020
Contact:

O & P Institutional Ethics Committe, 2 Floor,1671-75,Ganeshkhind Road, Shivajinagar,Pune-411005

Status: Approved
Approval date: 22/06/2020
Contact:

Institutional Ethics Committee, The Madras Medical Mission, 4-a, Dr.J.J.Nagar, Mogappair, Chennai - 600037, Tamilnadu, India