Hypertension
Conditions
Brief summary
To demonstrate that a fixed-dose combination of telmisartan 40 mg plus amlodipine 5 mg is superior to amlodipine 5 mg alone in patients with essential hypertension and inadequately controlled with amlodipine 5 mg monotherapy.
Interventions
DRUGamlodipine
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Essential hypertensive patients satisfying all of the following criteria; 2. Male or Female 3. Age \> 20 years 4. Outpatient 5. Patients who are able to stop current anti-hypertensive therapy at Visit 1 if taking any anti-hypertensive medications 6. Patients with an ability to provide written informed consent in accordance with the related laws and guidelines such as Good Clinical Practice (GCP) and the Pharmaceutical Affairs Law.
Exclusion criteria
1. Taking four or more anti-hypertensive medications 2. Secondary hypertension 3. Mean seated diastolic blood pressure (DBP) \> 114 mmHg and/or mean seated systolic blood pressure (SBP) \> 200 mmHg at Visit 1, 2, 3, or 4, or mean seated DBP \< 90 mmHg at Visit 3. 4. Sustained ventricular tachycardia or other clinically relevant cardiac arrhythmias 5. Congestive heart failure patients with the New York Heart Association (NYHA) functional class III-IV 6. History of myocardial infarction or cardiac surgery within last 6 months 7. History of coronary artery bypass graft or percutaneous coronary intervention (PCI) within last 3 months 8. History of unstable angina within last 3 months 9. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve 10. History of stroke or transient ischemic attack within last 6 months 11. History of sudden exacerbation of renal function with angiotensin II receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors, or patients with post-renal transplant or post-nephrectomy 12. Experienced characteristic symptoms of angioedema during treatment with ARBs or ACE inhibitors 13. Known hypersensitivity to any component of the investigational drug , or a known hypersensitivity to dihydropyridine -derived drugs 14. Hepatic and/or renal dysfunction 15. Diagnosed biliary atresia or cholestasis 16. Hyperkalemia 17. Dehydration 18. Sodium deficiency 19. Chronic administration of high doses of acidic nonsteroidal anti-inflammatory drugs (NSAIDs) 20. Patients who cannot change to the restricted administration and dosage during study period 21. Pre-menopausal women who meet any one of the following 1 - 3: * Pregnant or possibly pregnant (1) * Nursing (2) * Desire to become pregnant during study period (3) 22. Drug or alcohol dependency 23. Complication of malignant tumour or a disease requiring immunosuppressants 24. Compliance of \< 80% or \> 120% during the run-in period 25. Receiving any investigational therapy within 3 months 26. Judged to be inappropriate by the investigator or the sub-investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction From Reference Baseline in Mean Seated Diastolic Blood Pressure at Trough (24-hour Post-dosing) | Baseline and 8 Weeks | The mean of the change value was least square mean which was calculated by analysis of covariance with factor treatment and center, and covariate baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Seated Trough Diastolic Blood Pressure Less Than 90 mmHg at 8 Weeks (0 Percent at Baseline) | 8 weeks | Seated trough diastolic blood pressure defined as blood pressure in a sitting position no later than 24 hours after the last intake |
| Percentage of Patients With Seated Trough Systolic Blood Pressure Less Than 140 mmHg at 8 Weeks (0 Percent at Baseline) | 8 weeks | Seated trough systolic blood pressure defined as blood pressure in a sitting position no later than 24 hours after the last intake |
| Percentage of Patients Who Achieved an Adequate Response in Seated Trough Diastolic Blood Pressure at 8 Weeks (0 Percent at Baseline) | 8 weeks | Adequate response defined that seated trough diastolic blood pressure was \<90 mmHg or decreased from reference baseline by \>=10 mmHg at 8 weeks |
| Reduction From Reference Baseline in Mean Seated Systolic Blood Pressure at Trough (24-hour Post-dosing) | Baseline and 8 Weeks | The mean of the change value was least square mean which was calculated by analysis of covariance with factor treatment and center, and covariate baseline. |
| Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | 8 weeks | Optimal, normal, high normal blood pressure were defined as follows: * Optimal: Systolic blood pressure (SBP) \< 120 mmHg and diastolic blood pressure (DBP) \< 80 mmHg * Normal: SBP \>= 120 mmHg or DBP \>= 80 mmHg and SBP \< 130 mmHg and DBP \< 85 mmHg * High normal: SBP \>= 130 mmHg or DBP \>= 85 mmHg and SBP \< 140 mmHg and DBP \< 90 mmHg * No: SBP \>= 140 mmHg and DPB \>= 90 mmHg |
| Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | First administration of randomised treatment to 24 hours post last dose of randomised treatment | Clinical relevant abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
| Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks | 8 weeks | Adequate response defined that seated trough systolic blood pressure was \<140 mmHg or decreased from reference baseline by \>=20 mmHg at 8 weeks (0 percent at baseline) |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination T40/A5 tablet, oral, once daily in the morning | 269 |
| Amlodipine 5 mg Monotherapy A5 capsule, oral, once daily in the morning | 262 |
| Total | 531 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | No visit within allowance period | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Amlodipine 5 mg Monotherapy | Total |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 9.6 | 56 years STANDARD_DEVIATION 9.9 | 56.5 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 72 Participants | 76 Participants | 148 Participants |
| Sex: Female, Male Male | 197 Participants | 186 Participants | 383 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 269 | 34 / 262 |
| serious Total, serious adverse events | 1 / 269 | 2 / 262 |
Outcome results
Primary
Reduction From Reference Baseline in Mean Seated Diastolic Blood Pressure at Trough (24-hour Post-dosing)
The mean of the change value was least square mean which was calculated by analysis of covariance with factor treatment and center, and covariate baseline.
Time frame: Baseline and 8 Weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Reduction From Reference Baseline in Mean Seated Diastolic Blood Pressure at Trough (24-hour Post-dosing) | 9.56 mmHg | Standard Error 0.61 |
| Amlodipine 5 mg Monotherapy | Reduction From Reference Baseline in Mean Seated Diastolic Blood Pressure at Trough (24-hour Post-dosing) | 4.45 mmHg | Standard Error 0.61 |
p-value: <0.000195% CI: [3.98, 6.23]Mixed Models Analysis
Secondary
Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG
Clinical relevant abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time frame: First administration of randomised treatment to 24 hours post last dose of randomised treatment
Population: Treated set: Patients randomised to the double-blind treatment period who took at least one dose either of T40+A5 or A5 during the double-blind treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood creatine phosphokinase increased | 2 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood urine present | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Aspartate aminotransferase increased | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Liver function test abnormal | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood potassium increased | 0 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Bradycardia | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Alanine aminotransferase increased | 1 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Bradycardia | 0 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Alanine aminotransferase increased | 0 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Aspartate aminotransferase increased | 0 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood creatine phosphokinase increased | 0 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood potassium increased | 1 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Blood urine present | 0 participants |
| Amlodipine 5 mg Monotherapy | Clinically Relevant Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Liver function test abnormal | 0 participants |
Secondary
Percentage of Patients Who Achieved an Adequate Response in Seated Trough Diastolic Blood Pressure at 8 Weeks (0 Percent at Baseline)
Adequate response defined that seated trough diastolic blood pressure was \<90 mmHg or decreased from reference baseline by \>=10 mmHg at 8 weeks
Time frame: 8 weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Diastolic Blood Pressure at 8 Weeks (0 Percent at Baseline) | 74.5 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Diastolic Blood Pressure at 8 Weeks (0 Percent at Baseline) | 50.2 percentage of patients |
Secondary
Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks
Adequate response defined that seated trough systolic blood pressure was \<140 mmHg or decreased from reference baseline by \>=20 mmHg at 8 weeks (0 percent at baseline)
Time frame: 8 weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks | 79.5 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks | 58.4 percentage of patients |
Secondary
Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline)
Optimal, normal, high normal blood pressure were defined as follows: * Optimal: Systolic blood pressure (SBP) \< 120 mmHg and diastolic blood pressure (DBP) \< 80 mmHg * Normal: SBP \>= 120 mmHg or DBP \>= 80 mmHg and SBP \< 130 mmHg and DBP \< 85 mmHg * High normal: SBP \>= 130 mmHg or DBP \>= 85 mmHg and SBP \< 140 mmHg and DBP \< 90 mmHg * No: SBP \>= 140 mmHg and DPB \>= 90 mmHg
Time frame: 8 weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Optimal | 11.0 percentage of patients |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Normal | 24.3 percentage of patients |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | High Normal | 26.6 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Optimal | 1.6 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Normal | 9.7 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | High Normal | 23.0 percentage of patients |
Secondary
Percentage of Patients With Seated Trough Diastolic Blood Pressure Less Than 90 mmHg at 8 Weeks (0 Percent at Baseline)
Seated trough diastolic blood pressure defined as blood pressure in a sitting position no later than 24 hours after the last intake
Time frame: 8 weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients With Seated Trough Diastolic Blood Pressure Less Than 90 mmHg at 8 Weeks (0 Percent at Baseline) | 68.1 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients With Seated Trough Diastolic Blood Pressure Less Than 90 mmHg at 8 Weeks (0 Percent at Baseline) | 47.1 percentage of patients |
Secondary
Percentage of Patients With Seated Trough Systolic Blood Pressure Less Than 140 mmHg at 8 Weeks (0 Percent at Baseline)
Seated trough systolic blood pressure defined as blood pressure in a sitting position no later than 24 hours after the last intake
Time frame: 8 weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Percentage of Patients With Seated Trough Systolic Blood Pressure Less Than 140 mmHg at 8 Weeks (0 Percent at Baseline) | 67.1 percentage of patients |
| Amlodipine 5 mg Monotherapy | Percentage of Patients With Seated Trough Systolic Blood Pressure Less Than 140 mmHg at 8 Weeks (0 Percent at Baseline) | 45.8 percentage of patients |
Secondary
Reduction From Reference Baseline in Mean Seated Systolic Blood Pressure at Trough (24-hour Post-dosing)
The mean of the change value was least square mean which was calculated by analysis of covariance with factor treatment and center, and covariate baseline.
Time frame: Baseline and 8 Weeks
Population: Full analysis set for blood pressure measurements, which was the analysis set including all the patients who had valid measurements at the reference baseline and at one or more time-points after the start of the double-blind maintenance period on final dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Reduction From Reference Baseline in Mean Seated Systolic Blood Pressure at Trough (24-hour Post-dosing) | 13.04 mmHg | Standard Error 0.88 |
| Amlodipine 5 mg Monotherapy | Reduction From Reference Baseline in Mean Seated Systolic Blood Pressure at Trough (24-hour Post-dosing) | 5.77 mmHg | Standard Error 0.88 |