CTRI/2021/10/037500 [Registered on: 22/10/2021] Trial Registered Prospectively
Last Modified On:
05/04/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Bempedoic Acid Tablets in patients with high lipid levels and at high heart related risk.
Scientific Title of Study
“A Randomized, Double Blind, Double Dummy, Parallel Group, Active-Controlled, Comparative, Prospective, Multicenter and Phase III Clinical Study to Evaluate the Efficacy and Safety of Bempedoic Acid Tablets 180 mg in Patients with Hypercholesterolemia at High Cardiovascular Risk Inadequately Controlled by Maximally Tolerated Statin Therapy.â€
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
EP/BEM/CT/20/003
Protocol Number
Version No. 01 & Dated Sep 01, 2021
Other
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally, Hyderabad-500072,
Telangana, India.
Hyderabad TELANGANA 500072 India
Phone
7989233379
Fax
Email
dr.sekhar@clinwave.co.in
Details of Contact Person Scientific Query
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally, Hyderabad-500072,
Telangana, India.
Institutional Ethics Committee, Osmania Medical College and General Hospital
Approved
Institutional Ethics Committee, Ruby General Hospital
Approved
North East Healthcare Private Limited, W Pratiksha Hospital
Approved
Prakash Medical College Institutional Ethics Committee
Approved
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Kolhapur Institutional Ethics Committee 2 (RCSMGMCIEC2)
Approved
Redkar Hospital Institutional Ethics Committee (RHIEC), Redkar Hospital and Research Centre
Patients will be advised to take study drug orally once daily with or without food around same time every day for 12 weeks.
Study drug should be taken along with matching placebo of reference product preferably at the same time.
Comparator Agent
Ezetimibe Tablets 10 mg & Matching Placebo of Test Product
Patients will be advised to take study drug orally once daily with or without food around same time every day for 12 weeks.
Study drug should be taken along with matching placebo of test product preferably at the same time.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Male or Female patients aged between 18 to 75 (both inclusive) years.
2. Patient with Atherosclerotic Cardiovascular Disease (ASCVD) or Heterozygous Familial Hypercholesterolemia (HeFH) or both:
- Have ASCVD [with established Coronary Heart Disease (CHD) or CHD risk equivalents] > 3 months prior to screening
Documented history of CHD (includes 1 or more of the following):
- Acute MI
- Silent MI
- Unstable angina
- Coronary revascularization procedure (e.g., percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery)
- Clinically significant CHD diagnosed by invasive or non-invasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging)
- Documented CHD risk equivalents (includes 1 or more of the following criteria):
- Symptomatic peripheral arterial disease (PAD) defined as
- 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 computed tomographic angiography [CTA]) showing ≥50% stenosis or
- peripheral arterial revascularization (surgical or percutaneous) occurring greater than 90 days prior to Screening visit or
- abdominal aortic aneurysm confirmed by imaging or aortic aneurysm repair occurring greater than 90 days prior to Screening visit or
- lower extremity amputation due to peripheral vascular disease occurring greater than 90 days prior to Screening visit
- Cerebrovascular atherosclerotic disease defined by:
- ischemic stroke occurring greater than 90 days prior to Screening visit or
- Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a carotid artery determined by carotid ultrasound or angiogram occurring greater than 90 days prior to Screening visit.
3. Patients who are not able to achieve less than 70 mg/dl level of LDL-C despite being on 40 mg of Rosuvastatin or 80 mg of Atorvastatin for at least 6 weeks.
4. Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study. WOCBP must have a negative urine pregnancy test at screening / baseline visit.
5. Patients with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
6. Patients willing to comply with all the protocol related requirements.
ExclusionCriteria
Details
1. Patients with Total fasting (minimum of 10 hours) Triglycerides (TG) ≥500 mg/dL at screening visit.
2. Patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening visit.
3. Patients with the Body Mass Index (BMI) ≥ 40 kg/m2 at screening visit.
4. Patients with uncontrolled hypertension defined as sitting systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg at screening visit.
5. Patients with clinically significant impaired hepatic function (SGOT & SGPT ≥ 2X the UNL and/or Total bilirubin ≥ 1.2X the UNL) at screening visit.
6. Patients with uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5X the ULN at screening visit. Patients stabilized on thyroid replacement therapy for at least 6 weeks prior to randomization are allowed.
7. Patients with creatine kinase (CK) >3X ULN at screening visit.
8. Patients with Type 1 diabetes & Type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value ≥ 9%.
9. Patient with recent (within 3 months prior to the screening visit) uncontrolled or symptomatic cardiac arrhythmia (or medication for an arrhythmia that was started or dose changed within 3 months of screening), transient ischemic attack (TIA) or plans to undergo a major surgical or interventional procedure (e.g., PCI, CABG, carotid or peripheral revascularization) during study. Patients with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the Investigator to be stable for the previous 3 months from screening.
10. Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure.
11. Patient with Gastrointestinal conditions or procedures (including weight loss surgery; or gastric bypass) that may affect drug absorption.
12. Patients with history of nephritic syndrome or nephritis at screening.
13. Patients with Electrocardiographic abnormalities including conduction delay and an abnormal QTc interval.
14. Patients with a history of anaemia or haemoglobinopathy and/or haemoglobin < 10 g/dL for men; haemoglobin < 9 g/dL for women at screening.
15. Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.
16. Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
17. Patients with history of any malignancy.
18. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
19. Patients with Hyperuricemia.
20. Patients who have a history of tendon disorders or tendon rupture.
21. Patients with donation or transfusion of blood, plasma, or platelets within the past 30 days prior to screening.
22. Patients with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the patient’s participation in the study.
23. Patients with concurrent participation in another clinical trial within 90 days prior to signing informed consent.
24. Patients currently taking any of the prohibited medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
25. Suspected inability or unwillingness to comply with the study procedures.
26. Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Percent change from baseline to Week 12 in LDL-C.
Week 12
Secondary Outcome
Outcome
TimePoints
Percent change from baseline to Week 12 in non-HDL-C, TC, apoB, and hs-CRP.
Week 12
Absolute change from baseline to Week 12 in LDL-C.
Week 12
Adverse events / Serious adverse events reported during the study.
Week 4, Week 8 and Week 12
Changes in clinical laboratory parameters from baseline to end of the study visit (Week 12).
Baseline and Week 12
Target Sample Size
Total Sample Size="280" Sample Size from India="280" Final Enrollment numbers achieved (Total)= "294" Final Enrollment numbers achieved (India)="294"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
trial is a randomized, double blind, double dummy, parallel group, active-controlled,
comparative, prospective, multicenter and phase III clinical study to evaluate
the efficacy and safety of Bempedoic Acid Tablets 180 mg in patients with hypercholesterolemia
at high cardiovascular risk inadequately controlled by maximally tolerated statin
therapy.
Patients
who are willing and able to participate in the study will sign and date the informed
consent form on the day of screening / baseline visit (Visit 1). During this
screening period, patients who are willing to give consent will be evaluated
for all the eligibility criteria. Eligible patients (male or female) aged
between 18 to 75 years (both inclusive), history or diagnosis of atherosclerotic
cardiovascular disease or heterozygous familial hypercholesterolemia and who
are not able to achieve less than 70 mg/dl level of LDL-C despite being on 40
mg of Rosuvastatin or 80 mg of Atorvastatin for at least 6 weeks will be
considered for the study.
After confirming the inclusion/exclusion criteria the
subject will be randomized and provided with study medication at randomization
visit. Subjects will be provided with diary at randomization visit, which need
to be brought along with in each subsequent visit till the last visit. Follow
up visits will be done on week 4/day 28(±3), week 8/day 56(±3) and week 12/day 84(±3)
(Final Visit) of treatment to assess efficacy and safety.
Patients will be
assigned to either of the two arms i.e., Arm A or Arm B consisting of Bempedoic
Acid Tablets 180 mg or Ezetimibe Tablets 10 mg. Patients will be advised to
take study drug orally once daily with or without food around same time every
day for 12 weeks.