BETTER: This Study Will Assess the Response, Efficacy Compliance, and Inset of Action of Heart Rate Reduction of Bisoprolol (Nerkardou) (Between Low Dose and High Dose) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment In Egyptian Patients With Essential Hypertension.
Study Details
Study Description
Brief Summary
The goal of this prospective, open-label, single-arm interventional study is to Investigate the response, the efficacy of bisoprolol (Nerkardou)-(Oral Dissolvable Film) dosage form in treating patients with hypertension, measure patients' compliance to the (Oral Dissolvable Film) dosage form, especially being easy to carry and easy to use, and identify the onset of action of heart rate reduction.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 4 |
Detailed Description
The trial is designed to investigate the response of a single oral dose of bisoprolol ODF (investigational product) in the treatment of essential hypertension.
This is a Phase IV, open-label, single-arm, prospective trial where subjects will receive:
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Bisoprolol at an initial dose of 5 (mg) milligrams once daily for 2 weeks (Responders).
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If the blood pressure would be greater than or equal to 130/80 mmHg after 2 weeks, then the dose will be adjusted to 10 mg once daily (non-responders).
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The total duration of study treatment will be 12 weeks. (Flow chart of trail design Appendix III) and the total sample size of the study will be 827 participants.
Among responders, one oral dissolved film of 5 mg bisoprolol for 2 weeks will be administered.
After the assessment of the response rate for patients, Study medication will be tapered down and stopped after 2 weeks for responders.
A BP response is defined as a ≥20 mmHg decrease in sitting through SBP and a ≥10 mmHg decrease in sitting through DBP, or a sitting through SBP of <130 mmHg and a sitting through DBP of <80 mmHg. Patients who had ⩾a 10% decrease in HR will be considered to have an HR response.
Subsequently, non-responders (defined that those with BP ≥130/80 mmHg after 2 weeks) will be crossed over to the higher dose medication and in the following 10 weeks, the same procedures will be repeated. After 2 weeks, the non-responders will receive one oral dissolved film of 10 mg bisoprolol.
Drug administration will be done without food in the fasting state.
The trial has a duration of approximately 12 weeks, including:
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Screening (assessments to determine eligibility for entry into the trial, occurring on Day -7, and baseline visit on day 0)
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Period 1 for 5 mg bisoprolol (duration of 14 days; Day 1- Day 14)
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Period 2 for 10 mg bisoprolol (duration of 10 weeks; day 15 - to the end of week 12)
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Early withdrawal
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Follow-up (6 days; 6 consecutive visits occurring after week 12 through phone calls)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: (Nerkardou 5 mg) for period 1 & (Nerkardou 10 mg) for period 2 One ODF of bisoprolol 5 mg (Nerkardou 5 mg) Dosage form description: Bisoprolol oral dissolved film ODF: equivalent to 5 mg of bisoprolol fumarate. One ODF of bisoprolol 10 mg (Nerkardou 10 mg) Dosage form description: Bisoprolol oral dissolved film ODF: equivalent to 10 mg of bisoprolol fumarate. |
Drug: Nerkardou 5 mg & Nerkardou 10 mg
(Nerkardou 5 mg) Bisoprolol oral dissolved film ODF: equivalent to 5 mg of bisoprolol fumarate.
(Nerkardou 10 mg) Bisoprolol oral dissolved film ODF: equivalent to 10 mg of bisoprolol fumarate.
|
Outcome Measures
Primary Outcome Measures
- Investigation of the response to bisoprolol (Nerkardou) in treating patients with hypertension [At day 0 and day 14 post-treatment for 5 mg after the study duration (12 weeks) for 10 mg]
Measuring the response rate for patients. A Blood Pressure response is defined as a ≥20mmHg decrease in sitting through SBP and a ≥10mmHg decrease in sitting through DBP， or a sitting through SBP of <130mmHg and a sitting through DBP of <80mmHg. Patients who had ⩾a 10% decrease in HR will be considered to have an HR response Measuring the response rate for patients
Secondary Outcome Measures
- Measuring patients' compliance to this dosage form, especially being easy to carry and easy to use [On day 14 and after 3 months.]
Counting the returned doses each visit.
- Identifying the onset of action of heart rate reduction. [At day 0 and day 14 post-treatment for 5 mg after the study duration (12 weeks)]
Monitoring the onset of action of heart rate reduction after drug administration by measuring the difference in heart rate between each visit (the difference between the number of beats per minute between each visit and the subsequent one)
Eligibility Criteria
Criteria
Inclusion Criteria:
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The participant is willing and able to give informed consent for participation in the trial.
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Male or Female, aged 18 years or above.
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Body mass index (BMI) greater than or equal to 18 and below 32 kg/m2
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Newly diagnosed Hypertensive patients with stages 1 and 2 are defined according to the recent ESC/ESH guidelines as follows:
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Grade 1 hypertension: SBP 140 to 159mmHg and/or DBP 90 to 99mmHg
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Grade 2 hypertension: SBP 160 to 179mmHg and/or DBP 100 to 109mmHg at screening.
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Non-responders to the 1ST line of therapy for hypertension.
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Patients who can be safely switched to Bisoprolol according to PI decision.
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Healthy according to the assessment of the medical history, electrocardiogram (ECG), vital signs, physical examination, laboratory results, and negative serology tests (except results after vaccination).
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Each subject must be capable of understanding the trial procedures and sign the ICF before they participate in the trial.
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Subjects must consent to adhere to the recommended contraceptive methods as detailed in Appendix I.
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In the Investigator's opinion, is able and willing to comply with all trial requirements.
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Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.
Exclusion Criteria:
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A subject who cannot understand or does not agree with the study's contents.
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Grade III hypertension or malignant hypertension (Hypertensive crisis: Systolic over 180 and/or diastolic over 120).
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Subjects who are unable to discontinue all prior antihypertensive medications.
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Subjects with heart rates less than (<) 60 beats at rest
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Subjects with renal failure (serum creatinine > 2.0 milligram per decilitre [mg/dL])
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Subjects with unrecovered pulmonary edema
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Subjects have a history or currently have cardiovascular disease.
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Subjects with a history of cardiovascular surgeries.
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Subjects with a history of treated or untreated malignant tumors within the past 5 years
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Significant history of hypersensitivity to bisoprolol, amlodipine, other dihydropyridines, or any related products (including excipients of the formulations)
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Significant history of severe hypersensitivity reactions (e.g., angioedema) to any drugs
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Pulse rate (in supine position) less than 60 beats per minute (bpm) or more than 100 bpm at screening
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History or presence of peripheral arterial occlusion or Raynaud's syndrome
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Presence of diabetes mellitus
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History or presence of asthma
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Presence of significant gastrointestinal, liver, kidney disease, surgery, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects.
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Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and human immunodeficiency virus [HIV] antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, St. John's wort or other herbal medicine known with effect on CYP enzymes) within 28 days before Day 1 of this trial
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Acute conditions which might alter renal function (e.g., dehydration, severe infection)
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Surgery in the previous 28 days before Day 1 of this trial
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Any history of tuberculosis and/or prophylaxis for tuberculosis within 10 years of Day 1 of the trial
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Positive results to HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or treponema pallidum (TP) antibody tests
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Donation of 50 mL or more of blood within 28 days before Day 1 of the trial; donation of 500 mL or more of blood within 56 days before Day 1 of the trial
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History of suicidal tendency, history of, or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
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Positive pregnancy test (only for females of child-bearing potential), or females breastfeeding a child.
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Consumption of large quantities of methylxanthine-containing beverages (more than 600 mg caffeine/day: 1 cup (250 mL) of coffee contains approximately 100 mg of caffeine, 1 cup of black or green tea contains approximately 30 mg and 1 glass of cola contains approximately 20 mg caffeine)
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A participant with a life expectancy of fewer than 6 months, or inappropriate for the medication.
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Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
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Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genuine Research Center, Egypt
- Nerhadou International for pharmaceutical & Nutraceutical, Egypt
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Channaraya V, Marya RK, Somasundaram M, Mitra D, Tibrewala KD; BRIGHT investigators. Efficacy and tolerability of a beta-1 selective beta blocker, bisoprolol, as a first-line antihypertensive in Indian patients diagnosed with essential hypertension (BRIGHT): an open-label, multicentric observational study. BMJ Open. 2012 May 14;2(3):e000683. doi: 10.1136/bmjopen-2011-000683. Print 2012.
- Davidov ME, Singh SP, Vlachakis ND, Blumenthal JB, Simon JS, Bryzinski BS, Koury KJ, Alemayehu D. Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension. Clin Cardiol. 1994 May;17(5):263-8. doi: 10.1002/clc.4960170509.
- Gaziano TA, Opie LH, Weinstein MC. Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis. Lancet. 2006 Aug 19;368(9536):679-86. doi: 10.1016/S0140-6736(06)69252-0.
- Wee Y, Burns K, Bett N. Medical management of chronic stable angina. Aust Prescr. 2015 Aug;38(4):131-6. doi: 10.18773/austprescr.2015.042. Epub 2015 Aug 3.
- GRC/NE-CV/EG/39/IV