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

NCT ID: NCT05880056

Last Updated: 2024-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

406 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-08

Study Completion Date

2025-04-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Essential Hypertension

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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. Non responders patients on 10 mg will be shifted to other alternatives according to their merit and those patients will be included to intention to treat.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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(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.

Group Type EXPERIMENTAL

Nerkardou (5 mg) & (10 mg)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Bisoprolol oral dissolved film ODF (5 mg) & (10 mg)

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nerhadou International for pharmaceutical & Nutraceutical, Egypt

UNKNOWN

Sponsor Role collaborator

Genuine Research Center, Egypt

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bassem El-Zarif, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

National Heart Institute, Cairo, Egypt

Khaled AlKhashab, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Faculty of Medicine, Fayoum University Hospital, Egypt

Heba Hamdy, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Faculty of Medicine, Beni-Suef University Hospital, Egypt

Locations

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Al-Fayoum University Hospital

Al Fayyum, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Mohsen Fathallah, MD, Ph.D

Role: CONTACT

Telephone: +224514516

Sally Khairat, B.Sc.Pharma

Role: CONTACT

Telephone: +224514516

Facility Contacts

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Khaled Khashab, Professor

Role: primary

0105123662

Abdelrahman Gamal, assistant Lecturer

Role: backup

01032773645

References

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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.

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Related Links

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http://www.who.int/news-room/fact-sheets/detail/hypertension

Hypertension \[Internet\]. World Health Organization. 2023 \[cited 2023 Dec 13\].

http://www.who.int/data/gho/indicator-metadata-registry/imr-details/3236

Raised cholesterol \[Internet\]. World Health Organization. \[cited 2023 Dec 13\]

Other Identifiers

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GRC/NE-CV/EG/39/IV

Identifier Type: -

Identifier Source: org_study_id

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