Study of Bisoprolol (Nerkardou - Nerhadou International) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment in Egyptian Patients With Essential Hypertension (BETTER)

August 15, 2024 updated by: Genuine Research Center, Egypt

A Prospective, Multicenter, Open-label, Single-arm Interventional Study of Bisoprolol (Nerkardou - Nerhadou International) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment in Egyptian Patients With Essential Hypertension

The trial is designed to assess the safety and investigation of the efficacy of a single oral dose of bisoprolol (Nerkardou - Nerhadou) oral dissolvable film (ODF) 5 & 10 mg, and patients' compliance in the treatment of essential hypertension. This is a Phase IV, open-label, single-arm, prospective trial where subjects will receive:

  1. Bisoprolol (Nerkardou) at an initial dose of 5 (mg) milligrams once daily for 2 weeks.
  2. If the blood pressure would be greater than or equal to 130/80 mmHg after 2 weeks, then the dose will be titrated to 10 mg once daily (non-responders). Dose-Titration will be done at any follow-up visit based on the response.
  3. The total duration of study treatment will be 12 weeks ±2 days, and the total sample size of the study will be 406 participants.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The trial is designed to assess the safety and investigation of the efficacy of a single oral dose of bisoprolol (Nerkardou - Nerhadou) oral dissolvable film (ODF) 5 & 10 mg & patients' compliance in the treatment of essential hypertension. This is a Phase IV, open-label, single-arm, prospective trial where subjects will receive:

The subject will initially administer once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) for 2 weeks. After the assessment of the subject being a responder, study medication will be maintained till week 12. Response will be assessed for each patient every 2 weeks and dose-titration will be done based on the response and PI decision at any visit. Then, for responders, once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF will be administered for the subsequent 2 weeks. For non-responders once daily 10 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) will be administered for the subsequent 2 weeks. For those who are still not responding to the higher dose will be shifted to other alternatives according to their merit and they will be included to intention to treat.

A responder is defined by BP response, which is represented in the form of a ≥20 mmHg decreases in sitting through SBP and a ≥10 mmHg decreases in sitting through DBP, or a sitting through SBP of <130 mmHg and a sitting through DBP of <80 mmHg.

The total duration of study treatment will be 12 week (±2days). (Flow chart of trail design Appendix III) and the total sample size of the study will be 406 participants.

The trial has a duration of approximately 14 weeks, including:

  1. Screening (assessments to determine eligibility for entry into the trial, occurring within 14 days to day 1 before treatment initiation (week -2) to (week 0).
  2. Treatment duration (5 mg or 10 mg bisoprolol (Nerkardou) based on the response) (duration of 12 weeks); from Day 1 (week 1) to the end of day 84 ±2days (week 12 ±2days)
  3. Premature withdrawal/ Early Discontinuation

Study Type

Interventional

Enrollment (Estimated)

406

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Al Fayyūm, Egypt, 63611
        • Recruiting
        • Al-Fayoum University Hospital
        • Contact:
          • Khaled Khashab, Professor
          • Phone Number: 0105123662
        • Contact:
          • Abdelrahman Gamal, assistant Lecturer
          • Phone Number: 01032773645

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The participant is willing and able to give informed consent for participation in the trial.
  2. Male or Female, aged ≥ 21 and < 65 years.
  3. The subject with Body mass index (BMI) greater than or equal to 18.5 and below 30 kg/m2

  4. Newly diagnosed hypertensive patients with grade 1 and 2 are defined according to the recent ESC/ESH guidelines as follows:

    • Grade 1 hypertension: SBP 140 to 159mmHg and/or DBP 90 to 99mmHg
    • Grade 2 hypertension: SBP 160 to 179mmHg and/or DBP 100 to 109mmHg at screening.
  5. Non-responders to the 1ST line of therapy for hypertension other than beta blocker and can be safely switched to Bisoprolol (Nerkardou) according to PI decision.
  6. Subject doesn't have other comorbidity according to the assessment of the medical history, electrocardiogram (ECG), echocardiogram vital signs, physical examination, and laboratory results.
  7. Subject with heart rate (HR) ≥ 80 (BPM) at baseline.
  8. Female subjects in childbearing period, and not on a reliable contraceptive method must adhere to the recommended contraceptive methods as detailed in Appendix I.
  9. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

Exclusion Criteria:

  1. Grade III hypertension or malignant hypertension (Hypertensive crisis: Systolic over 180 and/or diastolic over 120).
  2. Subjects who are not legible to discontinue current antihypertensives such as calcium channel blockers (CCB), ACE- inhibitors, or diuretics for reasons other than hypertension, or responders to current therapy.
  3. Subjects with heart rates less than (<)80 beats at rest.
  4. Subjects with renal impairment (serum creatinine > 2.0 milligram per deciliter [mg/dL])
  5. Subjects with unrecovered pulmonary edema
  6. Subjects with a history of cardiovascular surgeries.
  7. Significant history of hypersensitivity to bisoprolol, amlodipine, other dihydropyridines, or any related products (including excipients of the formulations)
  8. Presence of diabetes mellitus
  9. History or presence of asthma
  10. 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.
  11. 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
  12. Acute conditions which might alter renal function (e.g., dehydration, severe infection)
  13. History of suicidal tendency, history of, or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
  14. Positive pregnancy test (only for females of child-bearing potential), or females breastfeeding a child.
  15. 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)
  16. A participant with a life expectancy of fewer than 6 months, or inappropriate for the medication as defined in the Product Information such as acute heart failure or decompensation of heart insufficiency, that requires a therapy with inotropic agents; cardiogenic shock; AV block grade II or III, sick sinus syndrome, sinoatrial heart block; symptomatic bradycardia; symptomatic hypotonia; severe asthma bronchiolus or severe chronic obstructive airways disease; advanced stages of peripheral arterial disease or Raynaud's Syndrome; untreated pheochromocytoma, metabolic acidosis.
  17. Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: (Nerkardou 5 mg) & (Nerkardou 10 mg)

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) & (10 mg)
Bisoprolol oral dissolved film ODF(5 mg): equivalent to 5 mg of bisoprolol fumarate Bisoprolol oral dissolved film ODF (10 mg): equivalent to 10 mg of bisoprolol fumarate.
Other Names:
  • Bisoprolol oral dissolved film ODF (5 mg) & (10 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The frequency of the first dose hypotension
Time Frame: At day 1 (week 1) within 1-4 hours of the first administration of 5& 10 mg doses
The frequency of occurrence of the first dose hypotension, which is defined as a fall in systolic blood pressure of 20 mm Hg or more, or to a systolic blood pressure of less than 100 mm Hg, with or without associated symptoms.
At day 1 (week 1) within 1-4 hours of the first administration of 5& 10 mg doses

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identifying Bradycardia manifestation Assess the safety of Nerkardou ODF.
Time Frame: At day 14±2 (week 2), day 28±2 (week 4), day 42± 2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Identify the number of patients with bradycardia manifestation, which is defined as heart rate reduction < 60 (bpm) after drug administration
At day 14±2 (week 2), day 28±2 (week 4), day 42± 2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Assess the safety of Nerkardou ODF.
Time Frame: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Number of reported AEs
At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Investigate the efficacy of (Nerkardou) in treating patients with hypertension
Time Frame: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Measuring the response rate for a patient's BP response, which 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
At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Investigate the overall response of (Nerkardou) in treating patients with hypertension
Time Frame: At the end of day 84±2 (week 12)
The change of systolic blood pressure from baseline will be measured. The change of diastolic blood pressure from baseline will be measured
At the end of day 84±2 (week 12)
Measuring Patients' compliance to this dosage form, especially being easy to carry and easy to use
Time Frame: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)
Doses returned will be counted at each visit.
At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genuine Research Center, Egypt

Collaborators

Nerhadou International for pharmaceutical & Nutraceutical, Egypt

Investigators

  • Principal Investigator: Bassem El-Zarif, MD, Ph.D, National Heart Institute, Cairo, Egypt
  • Principal Investigator: Khaled AlKhashab, MD, Ph.D, Faculty of Medicine, Fayoum University Hospital, Egypt
  • Principal Investigator: Heba Hamdy, MD, Ph.D, Faculty of Medicine, Beni-Suef University Hospital, Egypt

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 8, 2024

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

May 7, 2023

First Submitted That Met QC Criteria

May 18, 2023

First Posted (Actual)

May 30, 2023

Study Record Updates

Last Update Posted (Actual)

August 19, 2024

Last Update Submitted That Met QC Criteria

August 15, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GRC/NE-CV/EG/39/IV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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