Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bisoprolol/Amlodipine (Bisoprolol failed group) | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline | Baseline was defined as the latest SBP under monotherapy. | Baseline, Week 18 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment | Baseline was defined as the latest DBP before study treatment administration. | Baseline, Week 18 |
| Percentage of Subjects With Controlled Blood Pressure |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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
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
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Please contact the Merck KGaA Communication Center located in | Darmstadt | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27334671 | Derived | 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. |
Not provided
Not provided
A total of 200 subjects (100 subjects in the amlodipine failed group, and 100 subjects in the bisoprolol failed group) were enrolled and randomized in the trial. Out of which 196 subjects (97 subjects in amlodipine failed group and 99 subjects in bisoprolol failed group) were included in modified intent-to-treat (MITT) analysis set.
The study was conducted at 10 clinical trial sites in Guatemala.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Amlodipine Failed Group | Subjects who failed monotherapy with amlodipine 5 milligram (mg) before trial inclusion were randomized to amlodipine failed group to receive Bisoprolol/Amlodipine fixed dose combination(FDC) tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at initial dose of 5mg/5mg once daily for 6 weeks.If blood pressure (BP) was controlled at Week 6(Day 43),same dose continued for next 6 weeks. If BP was not controlled at Day 43,dose was increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks.Subjects who had controlled BP atWeek 12(Day 85),continued same dose that they were receiving for next 6 weeks. If BP was not controlled at Day 85,dose was increased to next level,(Bisoprolol/Amlodipine 5mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/5mg dose and Bisoprolol/Amlodipine 10mg/10mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18(Day 127).Controlled BP=Systolic BP(SBP)<140 millimetre of mercury(mmHg) and Diastolic BP(DBP)<90mmHg. |
| FG001 | Bisoprolol Failed Group | Subjects who failed monotherapy with bisoprolol 5 mg before trial inclusion were randomized to bisoprolol failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5mg/10mg or 10mg/5mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was 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). Controlled BP = SBP <140 mmHg and DBP <90 mmHg. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
MITT analysis set was defined as all randomized and treated subjects with at least 1 SBP measurement after the date of first dose of investigational medicinal product (IMP).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Amlodipine Failed Group | Subjects who failed monotherapy with amlodipine 5 mg before trial inclusion were randomized to amlodipine failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5 mg/10 mg or 10 mg/5 mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was increased to the next level (Bisoprolol/Amlodipine 5 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/5 mg dose and Bisoprolol/Amlodipine and 10 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/10 mg dose) until Week 18 (Day 127). Controlled BP= SBP <140 mmHg and DBP <90 mmHg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline | Baseline was defined as the latest SBP under monotherapy. | 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. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | Baseline, Week 18 |
|
Baseline up to Day 127
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amlodipine Failed Group | Subjects who failed monotherapy with amlodipine 5 mg before trial inclusion were randomized to amlodipine failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5 mg/10 mg or 10 mg/5 mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was increased to the next level (Bisoprolol/Amlodipine 5 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/5 mg dose and Bisoprolol/Amlodipine and 10 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/10 mg dose) until Week 18 (Day 127). Controlled BP= SBP <140 mmHg and DBP <90 mmHg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 17.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | MedDRA 17.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D017298 | Bisoprolol |
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Bisoprolol/Amlodipine (Amlodipine failed group) | 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). |
|
|
| 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 | 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. | Baseline up to Day 127 (end of trial) |
| Protocol Violation |
|
| Death |
|
| Withdrew consent |
|
| Other |
|
| BG001 | Bisoprolol Failed Group | Subjects who failed monotherapy with bisoprolol 5 mg before trial inclusion were randomized to bisoprolol failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5 mg/10 mg or 10 mg/5 mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was increased to the next level (Bisoprolol/Amlodipine 5 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/5 mg dose and Bisoprolol/Amlodipine and 10 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5mg/10mg dose) until Week 18 (Day 127). Controlled BP= SBP <140 mmHg and DBP <90 mmHg. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| OG001 | Bisoprolol Failed Group | Subjects who failed monotherapy with bisoprolol 5 mg before trial inclusion were randomized to bisoprolol failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5 mg/10 mg or 10 mg/5 mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was increased to the next level (Bisoprolol/Amlodipine 5 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/5 mg dose and Bisoprolol/Amlodipine and 10 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/10 mg dose) until Week 18 (Day 127). Controlled BP= SBP <140 mmHg and DBP <90 mmHg. |
|
|
|
| Secondary | Change From Baseline in Diastolic Blood Pressure (DBP) After 18 Weeks of Treatment | Baseline was defined as the latest DBP before study treatment administration. | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 18 |
|
|
|
| Secondary | Percentage of Subjects With Controlled Blood Pressure | MITT analysis set included all randomized and treated subjects with at least 1 SBP measurement after the date of first dose of IMP. | Posted | Number | percentage of subjects | Baseline up to Week 18 |
|
|
|
| Secondary | Change From Baseline in Heart Rate (HR) After 18 Weeks of Treatment | Baseline was defined as the latest HR before study treatment administration | 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. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Week 18 |
|
|
|
| Secondary | 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. | Safety analysis set included all subjects who received at least 1 dose of IMP. | Posted | Number | subjects | Baseline up to Day 127 (end of trial) |
|
|
|
| 1 |
| 100 |
| 63 |
| 100 |
| EG001 | Bisoprolol Failed Group | Subjects who failed monotherapy with bisoprolol 5 mg before trial inclusion were randomized to bisoprolol failed group to receive Bisoprolol/Amlodipine FDC tablet. Bisoprolol/Amlodipine FDC tablet was orally administered at an initial dose of 5 mg/5 mg once daily for 6 weeks. If BP was controlled at Week 6 (Day 43), the same dose was continued for next 6 weeks. If the BP was not controlled at Day 43, the dose was increased to Bisoprolol/Amlodipine 5 mg/10 mg or 10 mg/5 mg for next 6 weeks. Subjects who had controlled BP at Week 12 (Day 85), continued with the same dose that they were receiving for next 6 weeks. If their BP was not controlled at Day 85, dose was increased to the next level (Bisoprolol/Amlodipine 5 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/5 mg dose and Bisoprolol/Amlodipine and 10 mg/10 mg for subjects receiving Bisoprolol/Amlodipine 5 mg/10 mg dose) until Week 18 (Day 127). Controlled BP= SBP <140 mmHg and DBP <90 mmHg. | 2 | 100 | 53 | 100 |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| Multiple injuries | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
Not provided
Not provided
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Week 18 |
|
| AEs leading to discontinuation |
|
| AEs leading to death |
|