Hypertension
Conditions
Brief summary
The primary objectives of this trial are (a) to demonstrate that the fixed-dose combination T40/A5 or the fixed-dose combination T80/A5 is superior in reducing blood pressure at eight weeks compared with A5 (b) to demonstrate that the fixed-dose combination T40/A5 or the fixed-dose combination T80/A5 is not inferior in reducing blood pressure at eight weeks compared with A10 and (c) to demonstrate that the incidence of oedema on the fixed-dose combination T40/A5 pooled with the fixed-dose combination T80/A5 is superior (less oedema) to A10 in patients who fail to respond adequately to six weeks treatment with A5.
Interventions
DRUGamlodipine
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. patients aged at least 18 years at the date of signing the consent form 2. diagnosis of essential hypertension and blood pressure not adequately controlled before enrolment in the study 3. failure to respond adequately to six weeks treatment with amlodipine 5 mg monotherapy 4. able to stop any current antihypertensive therapy without unacceptable risk to the patient (Investigator's decision) 5. willing and able to provide written informed consent (in accordance with Good Clinical Practice and local legislation).
Exclusion criteria
1. are not practising acceptable means of birth control or do not plan to continue using acceptable means of birth control throughout the study and do not agree to submit to pregnancy testing during participation in the trial. Acceptable methods of birth control include the transdermal patch, oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. 2. known or suspected secondary hypertension 3. mean seated systolic blood pressure (SBP) over 200 mmHg and/or mean seated diastolic blood pressure (DBP) over 120 mmHg at Visit 1 or 2 or mean seated SBP over 180 mmHg and/or mean seated DBP over 120 mmHg at the end of the run-in period (Visit 3) 4. any clinically significant hepatic impairment (e.g. clinically significant cholestasis, biliary obstructive disorder or hepatic insufficiency) 5. severe renal impairment (e.g. serum creatinine \>3.0 mg/dL or \>265 mcmol/L, known creatinine clearance \<30mL/min or clinical markers of severe renal impairment) 6. bilateral renal artery stenosis or renal artery stenosis in a solitary kidney or post-renal transplant 7. clinically relevant hyperkalaemia 8. uncorrected volume or sodium depletion. 9. primary aldosteronism. 10. hereditary fructose or lactose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP) | End of study (8 weeks or last value on treatment) | Change from baseline to the end of study in trough DBP |
| Number of Patients With Oedema | During randomised treatment period (8 weeks was the planned end of treatment, some of the measurements analysed as end of study can be at 4 weeks or at any point on randomised treatment) | Patients from the treated set who experienced at least one case of general oedema. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Seated DBP Response | End of study (8 weeks or last value on treatment) | The number of patients who reach the target DBP of \<90mmHg or had a reduction in DBP \>= 10mmHg |
| Trough Seated SBP Control | End of study (8 weeks or last value on treatment) | The number of patients who reach the target SBP of \<140mmHg |
| Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) | End of study (8 weeks or last value on treatment) | Change from baseline to the end of study in trough SBP |
| Trough Seated Blood Pressure (BP) Normality Classes | End of study (8 weeks or last value on treatment) | The number of patients who reach predefined BP categories: * Optimal - SBP\<120 and DBP\<80 mmHg * Normal - SBP\<130 and DBP\<85 mmHg * High-normal - SBP\<140 DBP\<90 mmHg * Stage 1 hypertension - SBP\<160 and DBP\<100 * Stage 2 hypertension SBP\>=160 and DBP\>=100 mmHg |
| Trough Seated SBP Response | End of study (8 weeks or last value on treatment) | The number of patients who reach the target SBP of \<140mmHg or had a reduction in SBP \>= 15 mmHg |
| Trough Seated Diastolic Blood Pressure Control | End of study (8 weeks or last value on treatment) | The number of patients who reach the target DBP of \<90mmHg |
Countries
Belgium, Canada, Denmark, Finland, France, Netherlands, Norway, Philippines, South Africa, South Korea, Sweden, Taiwan
Participant flow
Pre-assignment details
1487 were enrolled, 1098 entered but 1 patient not treated.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine 5mg | 267 |
| Amlodipine 10mg | 276 |
| Telmisartan 40mg and Amlodipine 5mg | 277 |
| Telmisartan 80mg and Amlodipine 5mg | 277 |
| Total | 1,097 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 22 | 3 | 4 |
| Overall Study | Consent withdrawn | 2 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Non compliant with protocol | 1 | 0 | 0 | 3 |
| Overall Study | Other | 3 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Amlodipine 10mg | Amlodipine 5mg | Telmisartan 40mg and Amlodipine 5mg | Telmisartan 80mg and Amlodipine 5mg |
|---|---|---|---|---|---|
| Age, Continuous | 54.2 Years STANDARD_DEVIATION 10.6 | 54.3 Years STANDARD_DEVIATION 10.6 | 54 Years STANDARD_DEVIATION 10.6 | 53.9 Years STANDARD_DEVIATION 11 | 54.5 Years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 415 Participants | 100 Participants | 104 Participants | 117 Participants | 94 Participants |
| Sex: Female, Male Male | 682 Participants | 176 Participants | 163 Participants | 160 Participants | 183 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 | 22 / 267 | 74 / 276 | 14 / 277 | 10 / 277 |
| serious Total, serious adverse events | 2 / 267 | 1 / 276 | 2 / 277 | 1 / 277 |
Outcome results
Primary
Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP)
Change from baseline to the end of study in trough DBP
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 5mg | Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP) | -5.71 mmHg | Standard Error 0.49 |
| Amlodipine 10mg | Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP) | -7.95 mmHg | Standard Error 0.49 |
| Telmisartan 40mg and Amlodipine 5mg | Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP) | -9.35 mmHg | Standard Error 0.48 |
| Telmisartan 80mg and Amlodipine 5mg | Change From Baseline in Trough Seated Diastolic Blood Pressure (DBP) | -10.63 mmHg | Standard Error 0.48 |
p-value: <0.000195% CI: [-4.9, -2.38]ANCOVA
p-value: <0.000195% CI: [-6.18, -3.66]ANCOVA
95% CI: [-2.66, -0.14]ANCOVA
95% CI: [-3.93, -1.43]ANCOVA
Primary
Number of Patients With Oedema
Patients from the treated set who experienced at least one case of general oedema.
Time frame: During randomised treatment period (8 weeks was the planned end of treatment, some of the measurements analysed as end of study can be at 4 weeks or at any point on randomised treatment)
Population: The treated set (TS) consisted of all patients that took at least one dose of the double-blind treatment (n=1097)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Number of Patients With Oedema | Number of patients with any oedema | 23 patients |
| Amlodipine 5mg | Number of Patients With Oedema | Number of patients with general oedema | 23 patients |
| Amlodipine 10mg | Number of Patients With Oedema | Number of patients with general oedema | 75 patients |
| Amlodipine 10mg | Number of Patients With Oedema | Number of patients with any oedema | 76 patients |
| Telmisartan 40mg and Amlodipine 5mg | Number of Patients With Oedema | Number of patients with any oedema | 14 patients |
| Telmisartan 40mg and Amlodipine 5mg | Number of Patients With Oedema | Number of patients with general oedema | 14 patients |
| Telmisartan 80mg and Amlodipine 5mg | Number of Patients With Oedema | Number of patients with any oedema | 10 patients |
| Telmisartan 80mg and Amlodipine 5mg | Number of Patients With Oedema | Number of patients with general oedema | 10 patients |
Secondary
Change From Baseline in Trough Seated Systolic Blood Pressure (SBP)
Change from baseline to the end of study in trough SBP
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 5mg | Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) | -6.18 mmHg | Standard Error 0.73 |
| Amlodipine 10mg | Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) | -11.11 mmHg | Standard Error 0.72 |
| Telmisartan 40mg and Amlodipine 5mg | Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) | -13.56 mmHg | Standard Error 0.71 |
| Telmisartan 80mg and Amlodipine 5mg | Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) | -14.99 mmHg | Standard Error 0.71 |
Secondary
Trough Seated Blood Pressure (BP) Normality Classes
The number of patients who reach predefined BP categories: * Optimal - SBP\<120 and DBP\<80 mmHg * Normal - SBP\<130 and DBP\<85 mmHg * High-normal - SBP\<140 DBP\<90 mmHg * Stage 1 hypertension - SBP\<160 and DBP\<100 * Stage 2 hypertension SBP\>=160 and DBP\>=100 mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Normal | 23 patients |
| Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Optimal | 2 patients |
| Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | High-normal | 42 patients |
| Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 2 hypertension | 70 patients |
| Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 1 hypertension | 118 patients |
| Amlodipine 10mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 1 hypertension | 126 patients |
| Amlodipine 10mg | Trough Seated Blood Pressure (BP) Normality Classes | Optimal | 5 patients |
| Amlodipine 10mg | Trough Seated Blood Pressure (BP) Normality Classes | Normal | 30 patients |
| Amlodipine 10mg | Trough Seated Blood Pressure (BP) Normality Classes | High-normal | 68 patients |
| Amlodipine 10mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 2 hypertension | 32 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 2 hypertension | 26 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | High-normal | 63 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 1 hypertension | 127 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Optimal | 19 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Normal | 35 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 1 hypertension | 110 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Normal | 51 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | High-normal | 67 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Optimal | 21 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Blood Pressure (BP) Normality Classes | Stage 2 hypertension | 22 patients |
Secondary
Trough Seated DBP Response
The number of patients who reach the target DBP of \<90mmHg or had a reduction in DBP \>= 10mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Trough Seated DBP Response | Yes (Responder) | 116 patients |
| Amlodipine 5mg | Trough Seated DBP Response | No (Non-responder) | 139 patients |
| Amlodipine 10mg | Trough Seated DBP Response | No (Non-responder) | 98 patients |
| Amlodipine 10mg | Trough Seated DBP Response | Yes (Responder) | 163 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated DBP Response | Yes (Responder) | 177 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated DBP Response | No (Non-responder) | 93 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated DBP Response | Yes (Responder) | 187 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated DBP Response | No (Non-responder) | 84 patients |
Secondary
Trough Seated Diastolic Blood Pressure Control
The number of patients who reach the target DBP of \<90mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | Yes (DBP<90 mmHg) | 107 patients |
| Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | No (DBP>=90 mmHg) | 148 patients |
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control | No (DBP>=90 mmHg) | 113 patients |
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control | Yes (DBP<90 mmHg) | 148 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | Yes (DBP<90 mmHg) | 153 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | No (DBP>=90 mmHg) | 117 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | Yes (DBP<90 mmHg) | 173 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated Diastolic Blood Pressure Control | No (DBP>=90 mmHg) | 98 patients |
Secondary
Trough Seated SBP Control
The number of patients who reach the target SBP of \<140mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 100 patients |
| Amlodipine 5mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 155 patients |
| Amlodipine 10mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 119 patients |
| Amlodipine 10mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 142 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 162 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 108 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 178 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 93 patients |
Secondary
Trough Seated SBP Response
The number of patients who reach the target SBP of \<140mmHg or had a reduction in SBP \>= 15 mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward. The full analysis set included patients who had baseline and at least one post baseline trough measure of blood pressure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5mg | Trough Seated SBP Response | Yes (Responder) | 118 patients |
| Amlodipine 5mg | Trough Seated SBP Response | No (Non-responder) | 137 patients |
| Amlodipine 10mg | Trough Seated SBP Response | No (Non-responder) | 95 patients |
| Amlodipine 10mg | Trough Seated SBP Response | Yes (Responder) | 166 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated SBP Response | Yes (Responder) | 187 patients |
| Telmisartan 40mg and Amlodipine 5mg | Trough Seated SBP Response | No (Non-responder) | 83 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated SBP Response | Yes (Responder) | 200 patients |
| Telmisartan 80mg and Amlodipine 5mg | Trough Seated SBP Response | No (Non-responder) | 71 patients |