Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension

NCT ID: NCT01977794

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-03-31

Brief Summary

This is a randomized, comparative Phase 3 trial to investigate the efficacy of fixed dose combination (FDC) of bisoprolol and amlodipine in hypertensive subjects (superiority of FDC over monotherapies).

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bisoprolol failed group

Subjects who failed monotherapy with bisoprolol 5 milligram (mg) before trial inclusion will be randomized to bisoprolol failed group to receive Bisoprolol/Amlodipine FDC tablet

Group Type: EXPERIMENTAL

Bisoprolol/Amlodipine (Bisoprolol failed group)

Intervention Type: DRUG

Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If blood pressure (BP) is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).

Amlodipine failed group

Subjects who failed monotherapy with amlodipine 5 mg before trial inclusion will be randomized to amlodipine failed group to receive Bisoprolol/Amlodipine FDC tablet.

Group Type: EXPERIMENTAL

Bisoprolol/Amlodipine (Amlodipine failed group)

Intervention Type: DRUG

Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 milligram (mg)/5 mg once daily for 6 weeks. If BP is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).

Interventions

Bisoprolol/Amlodipine (Bisoprolol failed group)

Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If blood pressure (BP) is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).

Intervention Type: DRUG

Bisoprolol/Amlodipine (Amlodipine failed group)

Bisoprolol/Amlodipine FDC tablet will be orally administered at an initial dose of 5 milligram (mg)/5 mg once daily for 6 weeks. If BP is controlled at Week 6 (Day 43), the same dose will continue for next 6 weeks. If the BP is not controlled at Day 43, the dose will be increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who have controlled BP at Week 12 (Day 85), will continue with the same dose for next 6 weeks. If their BP is not controlled at Day 85, dose will be increased to the next level (Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine and 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127).

Intervention Type: DRUG

Other Intervention Names

Concor AM; Concor AM

Eligibility Criteria

Inclusion Criteria

• Essential hypertension not controlled at 5 mg bisoprolol or 5 mg amlodipine at least 4 weeks (definition of not controlled: SBP greater than or equal to (>=) 140 millimeter of mercury (mmHg) with or without DBP >= 90 mmHg)
• Male or female subjects >=18 years of age, without limitation on race
• Medically accepted effective contraception if procreative potential exists (applicable for both male and female subjects until at least 90 days after the last dose of trial treatment)
• Subjects who have signed the informed consent form before any trial related assessment

Exclusion Criteria

• General contraindications of beta-blockers and/or calcium channel blockers

• Previous and concurrent acute heart failure or during episodes of heart failure decompensation requiring intravenous inotropic therapy
• Concurrent cardiogenic shock
• Previous and concurrent second or third degree atrioventricular (AV) block (without a pacemaker)
• Previous and concurrent sick sinus syndrome
• Previous and concurrent sinoatrial block
• Concurrent symptomatic bradycardia
• Concurrent symptomatic hypotension
• Previous and concurrent severe bronchial asthma or chronic obstructive pulmonary diseases
• Previous and concurrent severe peripheral arterial occlusive diseases and Raynaud's syndrome
• Untreated pheochromocytoma
• Concurrent metabolic acidosis
• Known hypersensitivity to bisoprolol, amlodipine, dihydropyridine derivates or to any of the excipients
• Seated pulse rate less than 60 beats per minute (bpm) at screening
• Any other anti-hypertensive drugs (other than bisoprolol and amlodipine) are used within 4 weeks prior to the screening visit
• Use of any enzyme-modifying drugs acting on cytochrome P450 (CYP) 3A4 enzymes via inhibition (such as ketoconazole, itraconazole, ritonavir) or induction (such as rifampicin or hypericum perforatum) within 28 days before Day 1 of the trial
• Other significant disease that in the Investigator's opinion that would exclude the subject from the trial, such as uncontrolled diabetes mellitus, severe liver and/or kidney dysfunction, decompensated cardiac failure
• Any other condition or therapy which in the Investigator's opinion would pose a risk to the subject or interfere with the trial objectives
• Concurrent alcohol and/or drug abuse
• Known hypersensitivity to the trial treatments
• Pregnancy and lactation period. All female subjects with reproductive potential must have a negative pregnancy serum test within the 7 days prior to enrollment
• Known lack of subject compliance
• Legal incapacity or limited legal capacity
• Participation in another clinical trial within the previous 30 days
• Persons directly involved in the execution of the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Please contact the Merck KGaA Communication Center located in

Darmstadt, , Germany

Countries

Germany

References

Gottwald-Hostalek U, Li L, Montenegro P. Bisoprolol/amlodipine combination therapy improves blood pressure control in patients with essential hypertension following monotherapy failure. Curr Med Res Opin. 2016 Oct;32(10):1735-1743. doi: 10.1080/03007995.2016.1205573. Epub 2016 Jul 4.

Reference Type: DERIVED

PMID: 27334671 (View on PubMed)

Other Identifiers

200006-524

Identifier Type: -

Identifier Source: org_study_id