Clinical trial NCT01977794: Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension
Official title: A Randomized, Comparative Trial of Concor AM, a Fixed Dose Combination of Bisoprolol and Amlodipine, on the Treatment of Essential Hypertensive Patients Whose Blood Pressure is Not Well Controlled by Monotherapy of Bisoprolol 5mg or Amlodipine 5mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Bisoprolol
Amlodipine
Fixed dose combination (FDC)
Systolic Blood Pressure (SBP)
Diastolic Blood Pressure (DBP)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2013-11-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline
timeFrame: Baseline, Week 18
Secondary outcomes:
measure: Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment
timeFrame: Baseline, Week 18
measure: Percentage of Subjects With Controlled Blood Pressure
timeFrame: Baseline up to Week 18
measure: Change From Baseline in Heart Rate (HR) After 18 Weeks of Treatment
timeFrame: Baseline, Week 18
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Discontinuation and AEs Leading to Death
timeFrame: Baseline up to Day 127 (end of trial)
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center located in
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical responsible
role: STUDY_DIRECTOR
References:
citation: 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.