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

Phase 3

Completed

• Conditions: Hypertension
• Interventions: Drug: Bisoprolol/Amlodipine (Bisoprolol failed group); Drug: Bisoprolol/Amlodipine (Amlodipine failed group)

• Registration Number: NCT01977794
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-10-31
• Study First Submitted QC: 2013-10-31
• Study First Posted: 2013-11-07
• Study Start: 2014-03
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Results First Submitted: 2016-07-04
• Results First Submitted QC: 2016-07-04
• Results First Posted: 2016-08-11
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-12
• Last Update Posted: 2017-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bisoprolol failed group	Bisoprolol/Amlodipine (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
Amlodipine failed group	Bisoprolol/Amlodipine (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.

Primary Outcome Measures

Name	Time	Method
Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline	Baseline, Week 18	Baseline was defined as the latest SBP under monotherapy.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With Controlled Blood Pressure	Baseline up to Week 18
Change From Baseline in Heart Rate (HR) After 18 Weeks of Treatment	Baseline, Week 18	Baseline was defined as the latest HR before study treatment administration
Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment	Baseline, Week 18	Baseline was defined as the latest DBP before study treatment administration.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Discontinuation and AEs Leading to Death	Baseline up to Day 127 (end of trial)	An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs was AEs that started or worsened in severity on or after the date of first dose of IMP until the end of the study. AEs leading to death and discontinued were also presented.

Trial Locations

Locations (1)

Please contact the Merck KGaA Communication Center located in; 🇩🇪 Darmstadt, Germany