Hypertension
Conditions
Brief summary
If a patient cannot have his or her blood pressure controlled with telmisartan 80 mg, an antihypertensive drug from different class should be started concomitantly. In the Japanese 3x3 factorial trial of telmisartan and hydrochlorothiazide in essential hypertension patients whose diastolic blood pressure (DBP) are equal or more than 95 mmHg, the DBP control rate (less than 90 mmHg) after 8 weeks treatment of the telmisartan 80 mg monotherapy group (66 patients) was 41.5%. There should be medical needs of the telmisartan 80 mg and amlodipine 5 mg fixed dose combination because some patients cannot have his or her blood pressure controlled with telmisartan 80 mg. Thus, this clinical trial is being conducted to evaluate the antihypertensive effect and safety of a fixed-dose combination (FDC) drug of 2 antihypertensive agents with different pharmacological effects, telmisartan 80 mg and amlodipine 5 mg (T80/A5 mg), compared with telmisartan 80 mg (T80 mg) monotherapy in Japanese patients with essential hypertension who fail to respond adequately to treatment with the maximum dose of telmisartan 80 mg monotherapy. In this trial, a multi-centre, randomised, double-blind, double-dummy, active-controlled, parallel group comparison method is employed.
Interventions
Telmisartan 80 mg and amlodipine 5 mg once a daily
DRUGTelmisartan
80 mg once a daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Essential hypertensive patients * If already taking antihypertensive drugs, mean seated diastolic blood pressure (DBP) must be \>=90 and \>=114 mmHg * If not taking any antihypertensive drugs, mean seated DBP must be \>=95 and \>=114 mmHg * Able to stop all current antihypertensive drugs without risk to the patient based on the investigators opinion.
Exclusion criteria
* Patients taking 3 or more antihypertensive drugs at signing the informed consent form * Patients with known or suspected secondary hypertension * Patients with clinically relevant cardiac arrhythmia * Congestive heart failure with New York Heart Association (NYHA) functional class III-IV * Patients with recent cardiovascular events * Patients with a history of stroke or transient ischaemic attack within last 6 months before signing the informed consent form * Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors; or patients with post-renal transplant or post-nephrectomy * Patients who have previously experienced characteristic symptoms of angioedema (such as facial, tongue, pharyngeal, or laryngeal swelling with dyspnea) during treatment with ARBs or ACE inhibitors * Patients with known hypersensitivity to any component of the investigational product, or a known hypersensitivity to dihydropyridine-derived drugs * Patients with hepatic and/or renal dysfunction * Pre-menopausal women who are nursing or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | Baseline, 8 weeks | Reference baseline: Status of patients after the 8-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seated DBP Control Rate at Trough | 8 weeks | DBP control rate: The rate of patients with controlled seated DBP at trough of less than 90 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing |
| Seated SBP Control Rate at Trough | 8 weeks | SBP control rate: The rate of patients with controlled seated SBP at trough of less than 140 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing |
| Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | Baseline, 8 weeks | Reference baseline: Status of patients after the 8-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing |
| Seated SBP Response Rate at Trough | 8 weeks | SBP response rate: The rate of patients who achieved an adequate response in seated SBP at trough (\<140 mmHg and/or reduction from reference baseline ≥20 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing |
| Seated Blood Pressure (BP) Normalisation at Trough | 8 weeks | Seated blood pressure (BP) normalisation: The numbers of patients whose blood pressure was within normalisation criterion in terms of seated blood pressure after the 8-week double-blind period At trough: 24-hour post-dosing |
| Seated DBP Response Rate at Trough | 8 weeks | DBP response rate: The rate of patients who achieved an adequate response in seated DBP at trough (\<90 mmHg and/or reduction from reference baseline ≥10 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan and Amlodipine FDC | 87 |
| Telmisartan | 87 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period | Adverse Event | 0 | 1 |
| Double-blind Period | Lack of Efficacy | 0 | 1 |
| Double-blind Period | Study medication stolen | 1 | 0 |
| Open-label run-in Period | Blood pressure criteria not met | 0 | 18 |
| Open-label run-in Period | Number of patients fulfilled | 0 | 3 |
| Open-label run-in Period | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Telmisartan and Amlodipine FDC | Telmisartan | Total |
|---|---|---|---|
| Age, Continuous | 54.5 year STANDARD_DEVIATION 9 | 54.8 year STANDARD_DEVIATION 8.6 | 54.6 year STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 20 Participants | 13 Participants | 33 Participants |
| Sex: Female, Male Male | 67 Participants | 74 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 87 | 2 / 87 |
| serious Total, serious adverse events | 0 / 87 | 0 / 87 |
Outcome results
Primary
Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough
Reference baseline: Status of patients after the 8-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing
Time frame: Baseline, 8 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | 12.28 mmHg | Standard Error 0.73 |
| Telmisartan | Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | 3.14 mmHg | Standard Error 0.74 |
p-value: <0.000195% CI: [7.09, 11.18]ANCOVA
Secondary
Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough
Reference baseline: Status of patients after the 8-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing
Time frame: Baseline, 8 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | 18.37 mmHg | Standard Error 1.1 |
| Telmisartan | Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | 3.49 mmHg | Standard Error 1.1 |
p-value: <0.000195% CI: [11.82, 17.94]ANCOVA
Secondary
Seated Blood Pressure (BP) Normalisation at Trough
Seated blood pressure (BP) normalisation: The numbers of patients whose blood pressure was within normalisation criterion in terms of seated blood pressure after the 8-week double-blind period At trough: 24-hour post-dosing
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | No | 28 Participants |
| Telmisartan and Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Optimal | 21 Participants |
| Telmisartan and Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Normal | 22 Participants |
| Telmisartan and Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | High-normal | 16 Participants |
| Telmisartan | Seated Blood Pressure (BP) Normalisation at Trough | High-normal | 11 Participants |
| Telmisartan | Seated Blood Pressure (BP) Normalisation at Trough | No | 66 Participants |
| Telmisartan | Seated Blood Pressure (BP) Normalisation at Trough | Normal | 7 Participants |
| Telmisartan | Seated Blood Pressure (BP) Normalisation at Trough | Optimal | 2 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Seated DBP Control Rate at Trough
DBP control rate: The rate of patients with controlled seated DBP at trough of less than 90 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Seated DBP Control Rate at Trough | No | 29.9 Percentage of participants |
| Telmisartan and Amlodipine FDC | Seated DBP Control Rate at Trough | Yes | 70.1 Percentage of participants |
| Telmisartan | Seated DBP Control Rate at Trough | No | 73.3 Percentage of participants |
| Telmisartan | Seated DBP Control Rate at Trough | Yes | 26.7 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Seated DBP Response Rate at Trough
DBP response rate: The rate of patients who achieved an adequate response in seated DBP at trough (\<90 mmHg and/or reduction from reference baseline ≥10 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Seated DBP Response Rate at Trough | No | 19.5 Percentage of participants |
| Telmisartan and Amlodipine FDC | Seated DBP Response Rate at Trough | Yes | 80.5 Percentage of participants |
| Telmisartan | Seated DBP Response Rate at Trough | No | 69.8 Percentage of participants |
| Telmisartan | Seated DBP Response Rate at Trough | Yes | 30.2 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Seated SBP Control Rate at Trough
SBP control rate: The rate of patients with controlled seated SBP at trough of less than 140 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing
Time frame: 8 weeks
Population: Patients included in FAS and with seated SBP ≥140 mmHg at reference baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Seated SBP Control Rate at Trough | No | 26.0 Percentage of participants |
| Telmisartan and Amlodipine FDC | Seated SBP Control Rate at Trough | Yes | 74.0 Percentage of participants |
| Telmisartan | Seated SBP Control Rate at Trough | No | 71.2 Percentage of participants |
| Telmisartan | Seated SBP Control Rate at Trough | Yes | 28.8 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Seated SBP Response Rate at Trough
SBP response rate: The rate of patients who achieved an adequate response in seated SBP at trough (\<140 mmHg and/or reduction from reference baseline ≥20 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan and Amlodipine FDC | Seated SBP Response Rate at Trough | No | 11.5 Percentage of participants |
| Telmisartan and Amlodipine FDC | Seated SBP Response Rate at Trough | Yes | 88.5 Percentage of participants |
| Telmisartan | Seated SBP Response Rate at Trough | No | 48.8 Percentage of participants |
| Telmisartan | Seated SBP Response Rate at Trough | Yes | 51.2 Percentage of participants |
p-value: <0.0001Fisher Exact