Hypertension
Conditions
Brief summary
This is a multi-centre, randomised, double-blind, active-controlled, parallel-group comparative trial to compare the fixed dose combination (FDC) of telmisartan 80 mg + hydrochlorothiazide 12.5 mg and amlodipine 5 mg (T80/A5/H12.5 mg) to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg (T80/H12.5 mg) in blood pressure lowering effect at week 8, the end of the double-blind period in essential hypertensive patients who fail to respond adequately to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg. Patients are assigned to one of the two groups after a 6-week open-label run-in period taking T80/H12.5 mg. In addition the long-term safety of telmisartan 80 mg+ amlodipine 5 mg+ hydrochlorothiazide 12.5 mg will be evaluated in a 52-week extension period. In the 52-week open label extension period patients who are assigned to the T80/A5/H12.5 mg group continue the T80/A5/H12.5 mg therapy, and patients who are assigned to the T80/ /H12.5 mg group change to the T80/A5/H12.5 mg therapy.
Interventions
DRUGplacebo
placebo matching amlodipine capsule
DRUGtelmisartan + HCTZ
FDC tablet
DRUGamlodipine
capsule
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Essential hypertensive patients who have already taking 2 or 3 antihypertensive drugs and mean seated diastolic blood pressure (DBP) must be \>=90 and \<=114 mmHg and mean seated systolic blood pressure (SBP) must be =\<200 mmHg 2. Able to stop all current antihypertensive drugs (other than study medication) from Visit 1b through the end of the trial without risk to the patient based on the investigator's opinion 3. Age 20 years or older
Exclusion criteria
1. Patients with known or suspected secondary hypertension 2. Patients with clinically relevant cardiac arrhythmia 3. Congestive heart failure with New York Heart Association (NYHA) functional class III-IV 4. Patients with recent cardiovascular events 5. Patients with recent stroke events 6. Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers or angiotensin converting enzyme inhibitors; or patients with post-renal transplant or post-nephrectomy 7. Patients with hepatic and/or renal dysfunction 8. Pre-menopausal women who are nursing or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | baseline and 8 weeks | Change from baseline in mean seated diastolic blood pressure (DBP) at trough (24-hour post dosing) after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | baseline and 8 weeks | Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
| The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period. | Double-blind and 8 weeks | The percentage of patients with DBP\<90 mmHg and SBP\<140 mmHg as seated blood pressure at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
| The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | Reference baseline (week 0) and week 60 (end of extension period) | The number of patients with DBP\<90 mmHg and SBP\<140 mmHg as seated blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
| Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Reference baseline (week 0) and week 60 (end of extension period) | Change from baseline in mean seated diastolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
| Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Reference baseline (week 0) and week 60 (end of extension period) | Change from baseline in mean seated systolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. |
Countries
Japan
Participant flow
Recruitment details
Of the 239 enrolled patients, 205 patients were entered in the run-in period and 132 were randomized. The remaining 107 patients were withdrawn from the trial before the randomization.
Pre-assignment details
An eight-week randomised, double-blind study with active-control and parallel-group comparison in Japanese patients plus 52 week extension period.
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan + HCTZ + Amlodipine telmisartan 80 mg + hydrochlorothiazide (HCTZ) 12.5 mg fixed dose combination (FDC) and amlodipine 5 mg capsule orally, once daily (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet) | 68 |
| Telmisartan + HCTZ + Placebo telmisartan 80 mg + HCTZ FDC tablet and placebo matching amlodipine 5 mg capsule orally, once daily (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet) | 64 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period (8 Weeks) | Adverse Event | 1 | 2 |
| Double-blind Period (8 Weeks) | Consent withdrawn not due to AEs | 1 | 1 |
| Double-blind Period (8 Weeks) | Personal reason | 1 | 0 |
| Extension Period (52 Weeks) | Adverse Event | 3 | 0 |
| Extension Period (52 Weeks) | Consent withdrawn not due to AEs | 0 | 2 |
| Extension Period (52 Weeks) | Personal reason | 1 | 1 |
Baseline characteristics
| Characteristic | Telmisartan + HCTZ + Amlodipine | Telmisartan + HCTZ + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.1 Years STANDARD_DEVIATION 10.2 | 54.4 Years STANDARD_DEVIATION 7.9 | 55.2 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 55 Participants | 49 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 68 | 6 / 64 | 26 / 65 | 16 / 61 |
| serious Total, serious adverse events | 0 / 68 | 0 / 64 | 2 / 65 | 2 / 61 |
Outcome results
Primary
Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period.
Change from baseline in mean seated diastolic blood pressure (DBP) at trough (24-hour post dosing) after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: baseline and 8 weeks
Population: Full analysis set (FAS) was, conforming to the intent-to-treat principle, defined as all patients i) included in the treated set; and ii) taking measurements of seated DBP at reference baseline and at 1 or more time points during the double-blind period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | -8.8 mmHg | Standard Error 0.8 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | -1.3 mmHg | Standard Error 0.8 |
p-value: <0.000195% CI: [-9.7, -5.3]LOCF-ANCOVA
Secondary
Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period.
Change from baseline in mean seated diastolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: Reference baseline (week 0) and week 60 (end of extension period)
Population: FAS in the extension period (FASEX OC) was defined as a collection of patients i) included in the FAS; ii) taking at least 1 dose of T80/A5/H12.5 mg in the extension period; and iii) taking measurements of seated DBP at reference baseline and at 1 or more time points in the extension period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Adjusted mean | -10.9 mmHg | Standard Error 1 |
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Mean | -11.4 mmHg | Standard Error 1 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Mean | -10.0 mmHg | Standard Error 1 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Adjusted mean | -10.5 mmHg | Standard Error 1 |
95% CI: [-3.1, 2.3]mixed-effects model repeated measures
Secondary
Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period.
Change from baseline in mean seated systolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: Reference baseline (week 0) and week 60 (end of extension period)
Population: FASEX (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Mean | -14.8 mmHg | Standard Error 1.6 |
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Adjusted mean | -13.6 mmHg | Standard Error 1.3 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Mean | -14.3 mmHg | Standard Error 1.6 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Adjusted mean | -15.9 mmHg | Standard Error 1.4 |
95% CI: [-1.5, 6.1]mixed-effects model repeated measures
Secondary
Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period.
Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: baseline and 8 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan + HCTZ + Amlodipine | Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | -10.6 mmHg | Standard Error 1.4 |
| Telmisartan + HCTZ + Placebo | Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | -2.1 mmHg | Standard Error 1.5 |
p-value: <0.000195% CI: [-12.7, -4.5]LOCF-ANCOVA
Secondary
The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period.
The number of patients with DBP\<90 mmHg and SBP\<140 mmHg as seated blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: Reference baseline (week 0) and week 60 (end of extension period)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan + HCTZ + Amlodipine | The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | Yes | 41 Participants |
| Telmisartan + HCTZ + Amlodipine | The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | No | 24 Participants |
| Telmisartan + HCTZ + Placebo | The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | Yes | 33 Participants |
| Telmisartan + HCTZ + Placebo | The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | No | 28 Participants |
Secondary
The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period.
The percentage of patients with DBP\<90 mmHg and SBP\<140 mmHg as seated blood pressure at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.
Time frame: Double-blind and 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan + HCTZ + Amlodipine | The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period. | 44.8 Participants |
| Telmisartan + HCTZ + Placebo | The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period. | 21.9 Participants |
p-value: 0.005295% CI: [1.4, 7.1]Regression, Logistic