A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, COMPARATIVE, ACTIVE-CONTROLLED, PHASE III CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF FIXED-DOSE COMBINATION OF BISOPROLOL 5MG AND CILNIDIPINE 10MG TABLET VERSUS FIXED-DOSE COMBINATION OF METOPROLOL SUCCINATE ER 50MG AND CILNIDIPINE 10MG IN SUBJECTS WITH ESSENTIAL HYPERTENSION.
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Unique Pharmaceutical Laboratories (a Division of J. B. Chemicals & Pharmaceuticals Ltd.)
- Enrollment
- 214
- Locations
- 5
- Primary Endpoint
- Reduction in mean seated systolic (SeSBP) blood pressure
Overview
Brief Summary
Hypertension is a major individualistic risk factor for coronary artery disease, stroke, and renal failure. Reducing blood pressure (BP) below the target goal is important to prevent cardiovascular and cerebrovascular events. Various kinds of antihypertensive drugs such as diuretics, calcium channel blockers, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin-receptor blockers (ARBs) is usually used to lower BP effectively.
Monotherapy achieves optimal guideline recommended blood pressure targets only in 20–30 percent of patients with most hypertensive patients requiring a combination of two or more BP-lowering drugs.
The American Society of Hypertension, in a recent position paper, suggested starting with a combination therapy in patients with uncomplicated stage -1 HTN, in particular when one agent will improve the adverse effects profile of the other. European guidelines on HTN and the Joint National Committee 8 (JNC 8) guidelines recommend use of low dose combination therapy to initiate treatment even for those with mild hypertension.Even though CCBs have a linear dose-response curve, there is enhanced synergistic effect on BP reduction when additional antihypertensive agent such as beta-blocker is added to CCB therapy rather than simply doubling its dose. This combination therapy produces a more pronounced reduction in both systolic and diastolic BP.Bisoprolol Fumarate is the fumarate salt of a synthetic phenoxy-2-propanol-derived cardio-selective beta-1 adrenergic receptor antagonist with antihypertensive and potential cardioprotective activities. Devoid of intrinsic sympathomimetic activity, bisoprolol selectively and competitively binds to and blocks beta-1 adrenergic receptors in the heart, decreasing cardiac contractility and rate, reducing cardiac output, and lowering blood pressure.
Cilnidipine is a dihydropyridine calcium antagonist. Compared with other calcium antagonists, Cilnidipine can act on the N-type calcium channel that exists in sympathetic nerve endings besides acting on L-type calcium channels. Cilnidipine has been classified as a fourth-generation CCB based on its actions on sympathetic neurotransmitter release.
In India, Bisoprolol and Cilnidipine are already approved and marketed. Therefore, considering the unmet need for an FDC and based on regulatory requirementUnique Pharmaceutical Laboratories (a Division Of J. B. Chemicals & Pharmaceuticals Limited) proposes the present study be conducted to generate data on the Indian population. The study design is a multi-centre study to evaluate efficacy and safety of fixed-dose combination (FDC) of Bisoprolol 5mg and Cilnidipine 10mg tablet in subjects with mild to moderate hypertension. The purpose of the present study is to demonstrate that a fixed-dose combination (FDC) of Bisoprolol 5mg and Cilnidipine 10mg tablet is efficacious and safe in Indian subjects with regard to the routine clinical setting.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- Participant, Investigator and Outcome Assessor Blinded
Eligibility Criteria
- Ages
- 18.00 Year(s) to 65.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •1.Male or female participants with age 18 years to 65 years (both inclusive) at the time of screening 2.Adult subjects who are capable of understanding and giving written informed consent and willing to comply with the study protocol 3.Subjects diagnosed with Essential Hypertension with the background of stable coronary artery disease (CAD) with mean seated SBP ranging between 140-180 mmHg and or mean seated DBP ranging between 90-110 mmHg. Mean seated BP is defined as the average of 3 seated BP measurements at any screening or re-screening visit.
- •4.Females of non-child bearing potential (surgically sterile or menopausal) OR females of child bearing potential using effective birth control measures and non-pregnant & non-lactating females.
Exclusion Criteria
- •1.Subjects previously sensitive to any of the ingredients of the fixed-dose combination under study or beta-blockers or angiotensin receptor blockers, 2.Subjects with clinically significant renal disorders •Estimated glomerular filtration rate: less than 60 mL^min per 1.73 m2) •Subjects with S.
- •Creatinine values and S.BUN values more than equal to 1.5 times the upper limit of normal.
- ••Subjects with abnormal lab values of Na+, K+, Mg++ and Uric acid.
- •[Normal range: Na+ = 135-145 mEq^L, K+ = 3.5-5.0 mmol^L, Mg++ = 1.8-2.2 mg^dL and Uric acid 3.5-7.2 mg^dL] 3.Subjects with past history or present symptoms of Bradycardia [Pulse rate less than 60bpm] at 2 out of 3 measurements either at Screening or Randomization 4.Subjects with hepatocellular insufficiency and in subjects with hepatic failure or active liver disease [abnormal Liver Function Test with values more than 2.5 times the upper limit of normal] 5.Subjects with clinically Endocrine system disorders •Subjects with abnormal Thyroid Function Test (TSH).
- ••Subjects with Type 1 Diabetes Mellitus.
- ••Subjects with Type 2 Diabetes Mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value greater than 8 percent.
- •6.Subjects with a known history of secondary or malignant hypertension, 7.Subjects with LVEF less than 40 percent on 2D Echo at Screening or Randomization (previous reports of upto 8 weeks is acceptable), 8.Any known cardiac disease or disorder in which any of the study medication is contra-indicated (e.g. severe bradycardia, heart block greater than a first degree or significant first-degree block, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome without pacemaker etc.) 9.Subjects with known significant respiratory or liver or kidney or neurological diseases or uncontrolled diabetes 10.Pregnant and lactating women or the women of child bearing age who are not practicing the effective means of contraception 11.Subjects otherwise judged to be inappropriate for inclusion in the study by the investigator’s judgment 12.Subjects who will receive some other drug during the study besides that in the protocol that could alter the pharmacokinetic or pharmacodynamic profile of the study drug 13.Subjects with known alcohol or drug abuse 14.Subjects with known History of HIV, Hepatitis B and Hepatitis C 15.Hemodynamically unstable subjects.
Outcomes
Primary Outcomes
Reduction in mean seated systolic (SeSBP) blood pressure
Time Frame: 12 weeks
Secondary Outcomes
- Reduction in mean seated diastolic (SeDBP) blood pressure(12 weeks)
- Reduction in mean seated systolic (SeSBP) and seated diastolic (SeDBP) blood(4 weeks)
- Reduction in mean seated systolic (SeSBP) and seated diastolic (SeDBP) blood pressure(8 weeks)
- Percentage of the subjects achieving target clinical levels of mean seated systolic (SeSBP) blood pressure (target level: SeSBP less than 140 mm Hg)(4, 8 and 12 weeks)
- Percentage of the subjects achieving target clinical levels of mean seated diastolic (SeDBP) blood pressure (target level: SeDBP less than 90 mm Hg)(4, 8 and 12 weeks)
- Proportion of responders(12 weeks)
- Reduction in mean heart rate compared to baseline(4, 8 and 12 weeks)
Investigators
Mr Kartik Sahni
Insignia Clinical Services Pvt. Ltd.