Hypertension
Conditions
Brief summary
Blood pressure in hypertensive patients is rarely controlled to an optimal level by one drug alone, often a combination of two or more drugs is essential to achieve a sufficient antihypertensive effect. Therefore in Japanese Society of Hypertension (JSH) 2009 combination therapy is recommended. In JSH 2009 it is advised to start the combination therapy at a low dose, and to increase the dosage when the antihypertensive effect is not sufficient. In the Japanese long-term safety study, 259 patients received the T40/A5 mg fixed-dose combination (FDC), and after 6 weeks treatment 48 patients of them could not control their blood pressure (DBP =90) (U09-2494-01). For those patients who cannot control their blood pressure with T40/A5 mg FDC, a switch to a higher dose such as T80/A5 mg is recommended. In the overseas 4x4 factorial design trial, a clinically meaningful difference of the blood pressure lowering effect between T80/A5 mg free combination and T40/A5 mg free combination was shown (U07-3503-02). But the sponsor has no data that verifies this difference in Japanese patients. Thus, this clinical trial is being conducted to investigate the antihypertensive effect and safety of high dose T80/A5 mg FDC compared with low dose T40/A5 mg FDC in Japanese patients with essential hypertension. In this trial, a multi-centre, randomised, double-blind, double-dummy, active-controlled, parallel group comparison method is employed.
Interventions
DRUG40 mg telmisartan
once daily
DRUG5 mg amlodipine
once daily
DRUG80 mg telmisartan
once 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
Inclusion criteria
1. 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 2. Able to stop all current antihypertensive drugs without risk to the patient based on the investigators opinion.
Exclusion criteria
1. Patients taking 3 or more antihypertensive drugs at signing the informed consent form 2. Patients with known or suspected secondary hypertension 3. Patients with clinically relevant cardiac arrhythmia 4. Congestive heart failure with New York Heart Association (NYHA) functional class III-IV 5. Patients with recent cardiovascular events 6. Patients with a history of stroke or transient ischaemic attack within last 6 months before signing the informed consent form 7. 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 8. 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 9. Patients with known hypersensitivity to any component of the investigational product, or a known hypersensitivity to dihydropyridine-derived drugs 10. Patients with hepatic and/or renal dysfunction 11. 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 | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From the Reference Baseline in the 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean (Relative to Dose Time) for DBP | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined |
| Changes From the Reference Baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined |
| Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for DBP | Pseudo-baseline, 14 weeks | Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined |
| Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | Pseudo-baseline, 14 weeks | Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined |
| Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined |
| Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing |
| 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 DBP at trough of less than 140 mmHg 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 |
| 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 |
| Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Reference baseline, 8 weeks | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | 112 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | 113 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | 80 mg Telmisartan and 5 mg Amlodipine FDC | 40 mg Telmisartan and 5 mg Amlodipine FDC | Total |
|---|---|---|---|
| Age, Continuous | 54.6 year STANDARD_DEVIATION 8.4 | 52.8 year STANDARD_DEVIATION 9.4 | 53.7 year STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 23 Participants | 24 Participants | 47 Participants |
| Sex: Female, Male Male | 89 Participants | 89 Participants | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 112 | 6 / 113 |
| serious Total, serious adverse events | 1 / 112 | 1 / 113 |
Outcome results
Primary
Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing
Time frame: Reference baseline, 8 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | 4.93 mm Hg | Standard Error 0.61 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | 3.47 mm Hg | Standard Error 0.61 |
95% CI: [-0.22, 3.14]ANCOVA
Secondary
Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for DBP
Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Pseudo-baseline, 14 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for DBP | -12.16 mm Hg | Standard Error 0.61 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for DBP | -11.28 mm Hg | Standard Error 0.6 |
95% CI: [-2.57, 0.79]ANCOVA
Secondary
Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP
Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Pseudo-baseline, 14 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | -20.96 mm Hg | Standard Error 0.96 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | -19.32 mm Hg | Standard Error 0.95 |
95% CI: [-4.27, 0.99]ANCOVA
Secondary
Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Reference baseline, 8 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 7 | -0.40 mm Hg | Standard Deviation 12.24 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 2 | -1.95 mm Hg | Standard Deviation 11.44 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 3 | -2.25 mm Hg | Standard Deviation 11.86 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 4 | -3.69 mm Hg | Standard Deviation 12.43 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 5 | -1.39 mm Hg | Standard Deviation 13.22 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 6 | -1.58 mm Hg | Standard Deviation 11.08 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 1 | -1.04 mm Hg | Standard Deviation 10.27 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 8 | -1.58 mm Hg | Standard Deviation 13.23 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 9 | -2.77 mm Hg | Standard Deviation 12.83 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 10 | -2.80 mm Hg | Standard Deviation 13.75 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 11 | -1.47 mm Hg | Standard Deviation 11.58 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 12 | -0.74 mm Hg | Standard Deviation 11.86 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 13 | -2.33 mm Hg | Standard Deviation 12.96 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 14 | -0.53 mm Hg | Standard Deviation 15.49 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 15 | -0.36 mm Hg | Standard Deviation 13.65 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 16 | -0.01 mm Hg | Standard Deviation 10.73 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 17 | 0.70 mm Hg | Standard Deviation 12.16 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 18 | -1.89 mm Hg | Standard Deviation 11.81 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 19 | -3.12 mm Hg | Standard Deviation 12.96 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 20 | 0.23 mm Hg | Standard Deviation 11.03 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 21 | -3.25 mm Hg | Standard Deviation 12.85 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 22 | -2.00 mm Hg | Standard Deviation 11.83 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 23 | -2.07 mm Hg | Standard Deviation 12.05 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 24 | -0.82 mm Hg | Standard Deviation 9.37 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 23 | -0.53 mm Hg | Standard Deviation 11.95 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 1 | -0.22 mm Hg | Standard Deviation 12.38 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 13 | -1.05 mm Hg | Standard Deviation 12.03 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 2 | 0.32 mm Hg | Standard Deviation 10.93 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 19 | 0.10 mm Hg | Standard Deviation 10.38 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 3 | 2.87 mm Hg | Standard Deviation 11.61 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 14 | -0.08 mm Hg | Standard Deviation 11.36 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 4 | -0.02 mm Hg | Standard Deviation 10.63 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 22 | -1.67 mm Hg | Standard Deviation 13.14 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 5 | -0.75 mm Hg | Standard Deviation 14.06 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 15 | 1.86 mm Hg | Standard Deviation 10.88 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 6 | -0.86 mm Hg | Standard Deviation 13.32 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 20 | -1.27 mm Hg | Standard Deviation 11.93 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 7 | -1.25 mm Hg | Standard Deviation 13.22 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 16 | 0.85 mm Hg | Standard Deviation 10.97 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 8 | 0.55 mm Hg | Standard Deviation 13.83 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 24 | 0.42 mm Hg | Standard Deviation 11.23 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 9 | -0.73 mm Hg | Standard Deviation 12.44 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 17 | -0.80 mm Hg | Standard Deviation 11.07 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 10 | -0.14 mm Hg | Standard Deviation 11.58 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 21 | -0.90 mm Hg | Standard Deviation 10.81 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 11 | -1.16 mm Hg | Standard Deviation 12.05 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 18 | 1.02 mm Hg | Standard Deviation 10.33 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 12 | -1.43 mm Hg | Standard Deviation 13.65 |
Secondary
Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Reference baseline, 8 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 7 | -0.60 mm Hg | Standard Deviation 19.12 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 2 | -2.78 mm Hg | Standard Deviation 14.98 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 3 | -3.41 mm Hg | Standard Deviation 16.83 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 4 | -4.72 mm Hg | Standard Deviation 18.42 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 5 | -1.14 mm Hg | Standard Deviation 18.23 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 6 | -1.68 mm Hg | Standard Deviation 18.39 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 1 | -6.54 mm Hg | Standard Deviation 16.03 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 8 | -2.05 mm Hg | Standard Deviation 20.4 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 9 | -3.09 mm Hg | Standard Deviation 17.35 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 10 | -5.78 mm Hg | Standard Deviation 19.61 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 11 | -2.04 mm Hg | Standard Deviation 19.59 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 12 | -4.57 mm Hg | Standard Deviation 17.54 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 13 | -2.27 mm Hg | Standard Deviation 19.9 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 14 | -1.46 mm Hg | Standard Deviation 21.12 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 15 | -1.21 mm Hg | Standard Deviation 17.86 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 16 | -0.78 mm Hg | Standard Deviation 17.18 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 17 | -0.71 mm Hg | Standard Deviation 17.58 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 18 | -2.66 mm Hg | Standard Deviation 18.9 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 19 | -4.58 mm Hg | Standard Deviation 18.92 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 20 | 0.57 mm Hg | Standard Deviation 19.07 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 21 | -4.02 mm Hg | Standard Deviation 17.27 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 22 | -3.88 mm Hg | Standard Deviation 16.81 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 23 | -4.65 mm Hg | Standard Deviation 21.01 |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 24 | -2.24 mm Hg | Standard Deviation 16.51 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 23 | -2.71 mm Hg | Standard Deviation 16.15 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 1 | -1.78 mm Hg | Standard Deviation 16.37 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 13 | 0.26 mm Hg | Standard Deviation 17.53 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 2 | -0.28 mm Hg | Standard Deviation 15.82 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 19 | -1.24 mm Hg | Standard Deviation 15.3 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 3 | 2.72 mm Hg | Standard Deviation 17.74 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 14 | -1.09 mm Hg | Standard Deviation 17.49 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 4 | -1.88 mm Hg | Standard Deviation 17.03 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 22 | -4.12 mm Hg | Standard Deviation 17.4 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 5 | -2.54 mm Hg | Standard Deviation 20.71 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 15 | 1.41 mm Hg | Standard Deviation 17.7 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 6 | -2.48 mm Hg | Standard Deviation 20.01 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 20 | -3.56 mm Hg | Standard Deviation 17.02 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 7 | -2.45 mm Hg | Standard Deviation 18.69 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 16 | 0.68 mm Hg | Standard Deviation 15.42 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 8 | -0.27 mm Hg | Standard Deviation 22.07 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 24 | 0.29 mm Hg | Standard Deviation 16.09 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 9 | -1.17 mm Hg | Standard Deviation 18.33 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 17 | -1.16 mm Hg | Standard Deviation 15.67 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 10 | -0.70 mm Hg | Standard Deviation 18.91 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 21 | -1.20 mm Hg | Standard Deviation 16.47 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 11 | 0.69 mm Hg | Standard Deviation 15.16 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 18 | 1.01 mm Hg | Standard Deviation 15.84 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Hour 12 | 0.61 mm Hg | Standard Deviation 16.89 |
Secondary
Changes From the Reference Baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Reference baseline, 8 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | -2.81 mm Hg | Standard Error 0.81 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | -0.91 mm Hg | Standard Error 0.82 |
95% CI: [-4.16, 0.35]ANCOVA
Secondary
Changes From the Reference Baseline in the 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean (Relative to Dose Time) for DBP
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined
Time frame: Reference baseline, 8 weeks
Population: ABPM set, i.e., a subset of FAS and with patients who had available ABPM measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in the 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean (Relative to Dose Time) for DBP | -1.54 mm Hg | Standard Error 0.49 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Changes From the Reference Baseline in the 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean (Relative to Dose Time) for DBP | -0.33 mm Hg | Standard Error 0.49 |
95% CI: [-2.58, 0.15]ANCOVA
Secondary
Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough
Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing
Time frame: Reference baseline, 8 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | 5.55 mm Hg | Standard Error 0.9 |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | 3.41 mm Hg | Standard Error 0.91 |
95% CI: [-0.36, 4.64]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) |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Normal | 23 participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | No | 41 participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Optimal | 21 participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | High-normal | 27 participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | High-normal | 29 participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Normal | 26 participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | Optimal | 13 participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated Blood Pressure (BP) Normalisation at Trough | No | 44 participants |
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: Patients included in FAS and with seated DBP \>=90 mmHg at reference baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Control Rate at Trough | No | 53.1 percentage of participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Control Rate at Trough | Yes | 46.9 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Control Rate at Trough | No | 60.0 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Control Rate at Trough | Yes | 40.0 percentage of participants |
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) |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Response Rate at Trough | No | 29.5 percentage of participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Response Rate at Trough | Yes | 70.5 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Response Rate at Trough | No | 32.1 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated DBP Response Rate at Trough | Yes | 67.9 percentage of participants |
Secondary
Seated SBP Control Rate at Trough
SBP control rate: The rate of patients with controlled seated DBP 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) |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Control Rate at Trough | No | 55.2 percentage of participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Control Rate at Trough | Yes | 44.8 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Control Rate at Trough | No | 55.3 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Control Rate at Trough | Yes | 44.7 percentage of participants |
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) |
|---|---|---|---|
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Response Rate at Trough | No | 19.6 percentage of participants |
| 80 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Response Rate at Trough | Yes | 80.4 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Response Rate at Trough | No | 17.9 percentage of participants |
| 40 mg Telmisartan and 5 mg Amlodipine FDC | Seated SBP Response Rate at Trough | Yes | 82.1 percentage of participants |