HypertensionPhase 3NCT01977794

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

A Phase 3 study testing Bisoprolol/Amlodipine (Bisoprolol failed group) and Bisoprolol/Amlodipine (Amlodipine failed group) in people with Hypertension, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypertension
What is being tested?: Bisoprolol/Amlodipine (Bisoprolol failed group) and Bisoprolol/Amlodipine (Amlodipine failed group)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 1 siteGermany
Study dates: Mar 2014to Mar 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 25Show fewer

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Please contact the Merck KGaA Communication Center located in
Darmstadt

Other trials in Germany

About this study

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

Conditions: Hypertension
Being tested: Bisoprolol/Amlodipine (Bisoprolol failed group), Bisoprolol/Amlodipine (Amlodipine failed group)
Keywords: Bisoprolol, Amlodipine, Fixed dose combination (FDC), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bisoprolol/Amlodipine (Bisoprolol failed group)Drug
Also called Concor AM
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).
Bisoprolol/Amlodipine (Amlodipine failed group)Drug
Also called Concor AM
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).

Study groups in NCT01977794
Study group	Role	What they receive
Bisoprolol failed group	Experimental	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 Receives: Drug: Bisoprolol/Amlodipine (Bisoprolol failed group)
Amlodipine failed group	Experimental	Subjects who failed monotherapy with amlodipine 5 mg before trial inclusion will be randomized to amlodipine failed group to receive Bisoprolol/Amlodipine FDC tablet. Receives: Drug: Bisoprolol/Amlodipine (Amlodipine failed group)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (4)

Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment
Baseline was defined as the latest DBP before study treatment administration.
Measured: Baseline, Week 18
Percentage of Subjects With Controlled Blood Pressure
Measured: Baseline up to Week 18
Change From Baseline in Heart Rate (HR) After 18 Weeks of Treatment
Baseline was defined as the latest HR before study treatment administration
Measured: Baseline, Week 18
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Discontinuation and AEs Leading to Death
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.
Measured: Baseline up to Day 127 (end of trial)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2014Mar 2015

First posted7 Nov 2013 (estimated)
Study startMar 2014
Primary completionMar 2015
Study completionMar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 200 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01977794
Sponsor's protocol ID: 200006-524
Status last verified: Jan 2017
First submitted: 31 Oct 2013
Last updated: 30 Jan 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 27334671

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01977794
Acronym / sponsor ID: 200006-524
Conditions: Hypertension
Keywords: Bisoprolol, Amlodipine, Fixed dose combination (FDC), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 200 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: Mar 2014
Primary completion: Mar 2015 (actual)
Study completion: Mar 2015 (actual)
First posted: 7 Nov 2013 (estimated)
Results: Posted 11 Aug 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Bisoprolol failed group	Experimental	Drug: 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	Experimental	Drug: 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (25 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bisoprolol/Amlodipine (Bisoprolol failed group)Also: Concor AMBisoprolol/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).	Drug	Bisoprolol failed group
Bisoprolol/Amlodipine (Amlodipine failed group)Also: Concor AMBisoprolol/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).	Drug	Amlodipine failed group

Primary outcome

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

4 secondary outcomes

Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment
Time frame: Baseline, Week 18
Percentage of Subjects With Controlled Blood Pressure
Time frame: Baseline up to Week 18
Change From Baseline in Heart Rate (HR) After 18 Weeks of Treatment
Time frame: Baseline, Week 18
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Discontinuation and AEs Leading to Death
Time frame: Baseline up to Day 127 (end of trial)

Results and safety

Results posted to the registry on 11 Aug 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Amlodipine Failed Group	100	92
Bisoprolol Failed Group	100	94

Primary outcome: Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline

Time frame: Baseline, Week 18. Mean (Standard Deviation). Unit: millimeters of mercury (mmHg)

Measure	Amlodipine Failed Group n = 92	Bisoprolol Failed Group n = 94
Baseline	150.6 (8.21)	151.6 (11.57)
Change at Week 18	-24.7 (11.67)	-25.9 (12.82)

Amlodipine Failed Group vs Bisoprolol Failed Group: p <0.001, Paired t test

Population analysed: MITT analysis set was defined as all randomized and treated subjects with at least 1 SBP measurement after the date of first dose of IMP. Here "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to Day 127. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Amlodipine Failed Group	1 of 100 (1%)	63 of 100 (63%)	Not reported
Bisoprolol Failed Group	2 of 100 (2%)	53 of 100 (53%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27334671Gottwald-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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical responsible study director

Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline (time frame: Baseline, Week 18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01977794, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017; AzTrials last refreshed its copy on 8 Nov 2026.