Clinical trial NCT05880056: Study of Bisoprolol (Nerkardou - Nerhadou International) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment in Egyptian Patients With Essential Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Essential Hypertension
Lead sponsor: Genuine Research Center, Egypt
Sponsor class: INDUSTRY
Collaborators: name: Nerhadou International for pharmaceutical & Nutraceutical, Egypt
First posted: 2023-05-30
Enrollment: 406
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 purpose: TREATMENT

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. 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: The frequency of the first dose hypotension
timeFrame: At day 1 (week 1) within 1-4 hours of the first administration of 5& 10 mg doses
Secondary outcomes:
measure: Identifying Bradycardia manifestation Assess the safety of Nerkardou ODF.
timeFrame: 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)
measure: Assess the safety of Nerkardou ODF.
timeFrame: 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)
measure: Investigate the efficacy of (Nerkardou) in treating patients with hypertension
timeFrame: 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)
measure: Investigate the overall response of (Nerkardou) in treating patients with hypertension
timeFrame: At the end of day 84±2 (week 12)
measure: Measuring Patients' compliance to this dosage form, especially being easy to carry and easy to use
timeFrame: 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)
Other outcomes:
Locations:
city: Al Fayyūm
country: Egypt
facility: Al-Fayoum University Hospital
Study officials:
affiliation: National Heart Institute, Cairo, Egypt
name: Bassem El-Zarif, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculty of Medicine, Fayoum University Hospital, Egypt
name: Khaled AlKhashab, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculty of Medicine, Beni-Suef University Hospital, Egypt
name: Heba Hamdy, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
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