Hypertension
Conditions
Brief summary
The primary purpose of this study is to: Demonstrate that a fixed-dose combination of telmisartan 40 mg plus amlodipine 5 mg is superior to telmisartan 40 mg alone in patients with essential hypertension and inadequately controlled with telmisartan 40 mg monotherapy.
Interventions
DRUGtelmisartan
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 who satisfying non-responder criteria 2. Male or Female 3. Age 20 years or older 4. Outpatient
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 |
|---|---|---|
| Decrease in Seated Diastolic Blood Pressure From Baseline to 8 Weeks | 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 |
| Decrease in Seated Systolic Blood Pressure From Baseline to 8 Weeks | 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 |
| Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | First administration of randomised treatment to 24 hours post last dose of randomised treatment | Clinical relevant abnormalities for changes in blood pressure and pulse rate due to position change, seated 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 (0 Percent at Baseline) | 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 | 156 |
| Telmisartan 40 mg Monotherapy A5 capsule, oral, once daily in the morning | 158 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Not able to visit the site | 2 | 3 |
Baseline characteristics
| Characteristic | Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Telmisartan 40 mg Monotherapy | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 9.1 | 55.5 years STANDARD_DEVIATION 10.2 | 55.5 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 42 Participants | 35 Participants | 77 Participants |
| Sex: Female, Male Male | 114 Participants | 123 Participants | 237 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 156 | 16 / 158 |
| serious Total, serious adverse events | 1 / 156 | 0 / 158 |
Outcome results
Primary
Decrease in Seated Diastolic Blood Pressure From Baseline to 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.
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 | Decrease in Seated Diastolic Blood Pressure From Baseline to 8 Weeks | 13.49 mmHg | Standard Error 0.63 |
| Telmisartan 40 mg Monotherapy | Decrease in Seated Diastolic Blood Pressure From Baseline to 8 Weeks | 5.47 mmHg | Standard Error 0.62 |
p-value: <0.000195% CI: [6.41, 9.63]ANCOVA
Secondary
Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG
Clinical relevant abnormalities for changes in blood pressure and pulse rate due to position change, seated 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: Patients randomised to the double-blind treatment period who took at least one dose either of T40+A5 or T40 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 Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Blood potassium increased | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Eosinophil count increased | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Blood pressure increased | 0 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Orthostatic hypotension | 1 participants |
| Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Arrhythmia | 1 participants |
| Telmisartan 40 mg Monotherapy | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Orthostatic hypotension | 0 participants |
| Telmisartan 40 mg Monotherapy | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Arrhythmia | 0 participants |
| Telmisartan 40 mg Monotherapy | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Blood potassium increased | 0 participants |
| Telmisartan 40 mg Monotherapy | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Blood pressure increased | 2 participants |
| Telmisartan 40 mg Monotherapy | Clinically Relevant Abnormalities for Changes in Blood Pressure and Pulse Rate Due to Position Change, Seated Pulse Rate, Laboratory Parameters and ECG | Eosinophil count increased | 0 participants |
Secondary
Decrease in Seated Systolic Blood Pressure From Baseline to 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.
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 | Decrease in Seated Systolic Blood Pressure From Baseline to 8 Weeks | 17.86 mmHg | Standard Error 0.86 |
| Telmisartan 40 mg Monotherapy | Decrease in Seated Systolic Blood Pressure From Baseline to 8 Weeks | 6.51 mmHg | Standard Error 0.84 |
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) | 85 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Diastolic Blood Pressure at 8 Weeks (0 Percent at Baseline) | 50 percentage of participants |
Secondary
Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks (0 Percent at Baseline)
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 (0 Percent at Baseline) | 89.5 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients Who Achieved an Adequate Response in Seated Trough Systolic Blood Pressure at 8 Weeks (0 Percent at Baseline) | 58.2 percentage of participants |
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
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 | 17.0 percentage of participants |
| 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 | 30.7 percentage of participants |
| 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 | 26.1 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | High Normal | 17.1 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Optimal | 3.2 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients With Optimal, Normal or High Normal Blood Pressure at 8 Weeks (0 Percent at Baseline) | Normal | 17.1 percentage of participants |
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) | 78.4 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients With Seated Trough Diastolic Blood Pressure Less Than 90 mmHg at 8 Weeks (0 Percent at Baseline) | 46.8 percentage of participants |
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) | 81.2 percentage of participants |
| Telmisartan 40 mg Monotherapy | Percentage of Patients With Seated Trough Systolic Blood Pressure Less Than 140 mmHg at 8 Weeks (0 Percent at Baseline) | 37.1 percentage of participants |