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

NCT05880056 | Recruiting Phase 4

• 1 other identifier: GRC/NE-CV/EG/39/IV
• Study Type: interventional
• Target: 406
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Bisoprolol (Nerkardou) at an initial dose of 5 (mg) milligrams once daily for 2 weeks.
2. 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. 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.

Conditions

Essential Hypertension

Outcome Measures

Primary Outcomes (1)

• The frequency of the first dose hypotension

  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 Outcomes (5)

• Identifying Bradycardia manifestation Assess the safety of Nerkardou ODF.

  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.

  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

  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

  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

  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)

Study Arms (1)

(Nerkardou 5 mg) & (Nerkardou 10 mg)

EXPERIMENTAL

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)

Interventions

Nerkardou (5 mg) & (10 mg) 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.

Also known as: Bisoprolol oral dissolved film ODF (5 mg) & (10 mg)

(Nerkardou 5 mg) & (Nerkardou 10 mg)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant is willing and able to give informed consent for participation in the trial.
• Male or Female, aged ≥ 21 and \< 65 years.
• The subject with Body mass index (BMI) greater than or equal to 18.5 and below 30 kg/m2
• 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.
• 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.
• Subject doesn't have other comorbidity according to the assessment of the medical history, electrocardiogram (ECG), echocardiogram vital signs, physical examination, and laboratory results.
• Subject with heart rate (HR) ≥ 80 (BPM) at baseline.
• Female subjects in childbearing period, and not on a reliable contraceptive method must adhere to the recommended contraceptive methods as detailed in Appendix I.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

You may not qualify if:

• Grade III hypertension or malignant hypertension (Hypertensive crisis: Systolic over 180 and/or diastolic over 120).
• 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.
• Subjects with heart rates less than (\<)80 beats at rest.
• Subjects with renal impairment (serum creatinine \> 2.0 milligram per deciliter \[mg/dL\])
• Subjects with unrecovered pulmonary edema
• Subjects with a history of cardiovascular surgeries.
• Significant history of hypersensitivity to bisoprolol, amlodipine, other dihydropyridines, or any related products (including excipients of the formulations)
• Presence of diabetes mellitus
• History or presence of asthma
• 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.
• 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
• Acute conditions which might alter renal function (e.g., dehydration, severe infection)
• History of suicidal tendency, history of, or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
• Positive pregnancy test (only for females of child-bearing potential), or females breastfeeding a child.
• 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)

Sponsors & Collaborators

• Genuine Research Center, Egypt: lead
• Nerhadou International for pharmaceutical & Nutraceutical, Egypt: collaborator

Study Sites (1)

Al-Fayoum University Hospital

Al Fayyum, 63611, Egypt

RECRUITING

Related Publications (16)

• Fuchs FD, Whelton PK. High Blood Pressure and Cardiovascular Disease. Hypertension. 2020 Feb;75(2):285-292. doi: 10.1161/HYPERTENSIONAHA.119.14240. Epub 2019 Dec 23.

  PMID: 31865786 BACKGROUND

• NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep 11;398(10304):957-980. doi: 10.1016/S0140-6736(21)01330-1. Epub 2021 Aug 24.

  PMID: 34450083 BACKGROUND

• 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.

  PMID: 22586283 BACKGROUND

• Hostalek-Gottwald U, Gaciong Z. A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension. Curr Med Res Opin. 2022 Jul;38(7):1047-1053. doi: 10.1080/03007995.2022.2072087. Epub 2022 May 13.

  PMID: 35510372 BACKGROUND

• Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, Cifkova R, Clement D, Coca A, Dominiczak A, Erdine S, Fagard R, Farsang C, Grassi G, Haller H, Heagerty A, Kjeldsen SE, Kiowski W, Mallion JM, Manolis A, Narkiewicz K, Nilsson P, Olsen MH, Rahn KH, Redon J, Rodicio J, Ruilope L, Schmieder RE, Struijker-Boudier HA, Van Zwieten PA, Viigimaa M, Zanchetti A. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Blood Press. 2009;18(6):308-47. doi: 10.3109/08037050903450468. No abstract available.

  PMID: 20001654 BACKGROUND

• Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernandez-Alfonso MS, Halimi JM, Jarai Z, Jelakovic B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. doi: 10.1097/HJH.0000000000003480. Epub 2023 Sep 26.

  PMID: 37345492 BACKGROUND

• Deedwania P. Hypertension, dyslipidemia, and insulin resistance in patients with diabetes mellitus or the cardiometabolic syndrome: benefits of vasodilating beta-blockers. J Clin Hypertens (Greenwich). 2011 Jan;13(1):52-9. doi: 10.1111/j.1751-7176.2010.00386.x. Epub 2010 Nov 8.

  PMID: 21214722 BACKGROUND

• Prichard BN, Cruickshank JM, Graham BR. Beta-adrenergic blocking drugs in the treatment of hypertension. Blood Press. 2001;10(5-6):366-86. doi: 10.1080/080370501753400665.

  PMID: 11822540 BACKGROUND

• Dutta A, Lanc R, Begg E, Robson R, Sia L, Dukart G, Desjardins R, Yacobi A. Dose proportionality of bisoprolol enantiomers in humans after oral administration of the racemate. J Clin Pharmacol. 1994 Aug;34(8):829-36. doi: 10.1002/j.1552-4604.1994.tb02047.x.

  PMID: 7962671 BACKGROUND

• Minushkina LO. [Bisoprolol: opportunities in the treatment of hypertension]. Kardiologiia. 2012;52(6):80-5. Russian.

  PMID: 22839675 BACKGROUND

• 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.

  PMID: 26648642 BACKGROUND

• Johns TE, Lopez LM. Bisoprolol: is this just another beta-blocker for hypertension or angina? Ann Pharmacother. 1995 Apr;29(4):403-14. doi: 10.1177/106002809502900412.

  PMID: 7633020 BACKGROUND

• Lancaster SG, Sorkin EM. Bisoprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1988 Sep;36(3):256-85. doi: 10.2165/00003495-198836030-00002.

  PMID: 2903820 BACKGROUND

• Tjandrawinata RR, Setiawati E, Yunaidi DA, Santoso ID, Setiawati A, Susanto LW. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects. Drug Des Devel Ther. 2012;6:311-6. doi: 10.2147/DDDT.S36567. Epub 2012 Oct 30.

  PMID: 23139624 BACKGROUND

• Baxter AJ, Spensley A, Hildreth A, Karimova G, O'Connell JE, Gray CS. Beta blockers in older persons with heart failure: tolerability and impact on quality of life. Heart. 2002 Dec;88(6):611-4. doi: 10.1136/heart.88.6.611.

  PMID: 12433890 BACKGROUND

• 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.

  PMID: 8004841 BACKGROUND

Related Links

• Hypertension \[Internet\]. World Health Organization. 2023 \[cited 2023 Dec 13\].
• Raised cholesterol \[Internet\]. World Health Organization. \[cited 2023 Dec 13\]
• World Health Organization. Egypt STEPS Survey 2017. 2017
• Bisoprolol Pharmacokinetics

MeSH Terms

Conditions

Essential Hypertension

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohsen Fathallah, MD, Ph.D

CONTACT

Telephone: +224514516; mohsen.fathallah@grc-me.com

Sally Khairat, B.Sc.Pharma

CONTACT

Telephone: +224514516; sally.khairat@grc-me.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 7, 2023
• First Posted: May 30, 2023
• Study Start: August 8, 2024
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)