Hypertension
Conditions
Brief summary
The primary objectives of this trial is to demonstrate that the fixed-dose combination of telmisartan 80mg plus amlodipine 5mg (T80/A5) is superior to amlodipine 5mg (A5) in reducing seated trough diastolic blood pressure (DBP) at 8 weeks.
Interventions
DRUGTelmisartan80mg+Amlodipine5mg
combination therapy
DRUGamlodipine 5mg
monotherapy
DRUGTelmisartan80mg+Amlodipine 5mg
combination therapy
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. diagnosis of essential hypertension 2. failure to respond adequately to six weeks treatment with amlodipine 5 mg monotherapy 3. provision of written informed consent
Exclusion criteria
1\. clinical conditions which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of telmisartan and amlodipine for the planned duration of this trial (e.g. populations where labeling of either product recommends against its utilization)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in DBP After 8 Weeks of Treatment | Baseline and 8 weeks | Seated trough DBP after 8 weeks or last observation carried forward (LOCF). Analysis will be adjusted for treatment, country, and baseline measurement of endpoint. |
| Change From Baseline in DBP After 8 Weeks of Treatment in Chinese Patients | Baseline and 8 weeks | Seated trough DBP after 8 weeks or LOCF in Chinese patients. Analysis will be adjusted for treatment and baseline measurement of endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients in Blood Pressure Categories Over Time | 8 weeks | BP optimal: SBP \<120 mmHg and DBP \<80 mmHg, BP normal: SBP \<130 mmHg and DBP \<85 mmHg but not optimal, BP high-normal: SBP \<140 mmHg and DBP \<90 mmHg but not normal. Grade 1 hypertension: SBP \<160 mmHg and DBP \<100 mmHg but not high-normal, Grade 2 hypertension: SBP \<180 mmHg and DBP \<110 mmHg but not grade 1, Grade 3 hypertension: SBP \>=180 mmHg or DBP \>=110 mmHg. |
| Change From Baseline in DBP After 4 Weeks of Treatment | Baseline and 4 weeks | Seated trough DBP after 4 weeks. |
| Change From Baseline in SBP After 4 Weeks of Treatment | Baseline and 4 weeks | Seated trough SBP after 4 weeks. |
| Change From Baseline in SBP After 8 Weeks of Treatment | Baseline and 8 weeks | Seated trough SBP after 8 weeks or LOCF. Analysis will be adjusted for treatment, country, and baseline measurement of endpoint. |
| Number of Patients in Blood Pressure Categories at 4 Weeks | 4 weeks | BP optimal: SBP \<120 mmHg and DBP \<80 mmHg, BP normal: SBP \<130 mmHg and DBP \<85 mmHg but not optimal, BP high-normal: SBP \<140 mmHg and DBP \<90 mmHg but not normal. Grade 1 hypertension: SBP \<160 mmHg and DBP \<100 mmHg but not high-normal, Grade 2 hypertension: SBP \<180 mmHg and DBP \<110 mmHg but not grade 1, Grade 3 hypertension: SBP \>=180 mmHg or DBP \>=110 mmHg. |
| Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | From drug administration until end of treatment plus one day | Clinically relevant abnormalities for Physical examination, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
| DBP and SBP Control and Response After 4 Weeks of Treatment | Baseline and 4 weeks | DBP control is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment. SBP control is defined as SBP \<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment. DBP response is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=10mmHg. SBP response is defined as SBP\<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=15mmHg. |
| DBP and SBP Control and Response After 8 Weeks of Treatment | Baseline and 8 weeks | DBP control is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment. SBP control is defined as SBP \<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment. DBP response is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=10mmHg. SBP response is defined as SBP\<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=15mmHg. |
Countries
China, Malaysia, Philippines
Participant flow
Pre-assignment details
Whilst there were 324 patients randomised and treated, there were only 314 in the Full analysis set (FAS).
Participants by arm
| Arm | Count |
|---|---|
| A5 Alone Amlodipine 5mg monotherapy | 159 |
| T80/A5 Telmisartan 80mg plus Amlodipine 5mg fixed-dose combination | 155 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | A5 Alone | T80/A5 |
|---|---|---|---|
| Age, Continuous | 52.4 Years STANDARD_DEVIATION 9.2 | 52.4 Years STANDARD_DEVIATION 9.7 | 52.4 Years STANDARD_DEVIATION 8.7 |
| Diastolic blood pressure (DBP) | 97.53 mmHg STANDARD_DEVIATION 5.97 | 97.84 mmHg STANDARD_DEVIATION 6.43 | 97.21 mmHg STANDARD_DEVIATION 5.46 |
| Sex: Female, Male Female | 149 Participants | 71 Participants | 78 Participants |
| Sex: Female, Male Male | 165 Participants | 88 Participants | 77 Participants |
| Systolic blood pressure (SBP) | 146.35 mmHg STANDARD_DEVIATION 11.66 | 146.27 mmHg STANDARD_DEVIATION 11.15 | 146.44 mmHg STANDARD_DEVIATION 12.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 164 | 0 / 160 |
| serious Total, serious adverse events | 0 / 164 | 0 / 160 |
Outcome results
Primary
Change From Baseline in DBP After 8 Weeks of Treatment
Seated trough DBP after 8 weeks or last observation carried forward (LOCF). Analysis will be adjusted for treatment, country, and baseline measurement of endpoint.
Time frame: Baseline and 8 weeks
Population: Full analysis set (FAS) defined as patients randomised, treated, with a baseline endpoint measurement and at least one post-dose endpoint measurement during the double blind (DB) phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Alone | Change From Baseline in DBP After 8 Weeks of Treatment | -10.19 mmHg | Standard Error 0.93 |
| T80/A5 | Change From Baseline in DBP After 8 Weeks of Treatment | -12.38 mmHg | Standard Error 0.95 |
Comparison: A5 minus T80/A5p-value: 0.00795% CI: [0.6082, 3.7681]ANCOVA
Primary
Change From Baseline in DBP After 8 Weeks of Treatment in Chinese Patients
Seated trough DBP after 8 weeks or LOCF in Chinese patients. Analysis will be adjusted for treatment and baseline measurement of endpoint.
Time frame: Baseline and 8 weeks
Population: FAS with LOCF and further restricted to the Chinese subgroup
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Alone | Change From Baseline in DBP After 8 Weeks of Treatment in Chinese Patients | -8.85 mmHg | Standard Error 0.63 |
| T80/A5 | Change From Baseline in DBP After 8 Weeks of Treatment in Chinese Patients | -10.77 mmHg | Standard Error 0.64 |
Comparison: A5 minus T80/A5p-value: 0.03495% CI: [0.1443, 3.6947]ANCOVA
Secondary
Change From Baseline in DBP After 4 Weeks of Treatment
Seated trough DBP after 4 weeks.
Time frame: Baseline and 4 weeks
Population: FAS with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A5 Alone | Change From Baseline in DBP After 4 Weeks of Treatment | -7.51 mmHg | Standard Deviation 6.8 |
| T80/A5 | Change From Baseline in DBP After 4 Weeks of Treatment | -9.41 mmHg | Standard Deviation 7.26 |
Secondary
Change From Baseline in SBP After 4 Weeks of Treatment
Seated trough SBP after 4 weeks.
Time frame: Baseline and 4 weeks
Population: FAS with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A5 Alone | Change From Baseline in SBP After 4 Weeks of Treatment | -8.19 mmHg | Standard Deviation 11.45 |
| T80/A5 | Change From Baseline in SBP After 4 Weeks of Treatment | -12.10 mmHg | Standard Deviation 11.68 |
Secondary
Change From Baseline in SBP After 8 Weeks of Treatment
Seated trough SBP after 8 weeks or LOCF. Analysis will be adjusted for treatment, country, and baseline measurement of endpoint.
Time frame: Baseline and 8 weeks
Population: FAS with LOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Alone | Change From Baseline in SBP After 8 Weeks of Treatment | -11.66 mmHg | Standard Error 1.3 |
| T80/A5 | Change From Baseline in SBP After 8 Weeks of Treatment | -16.15 mmHg | Standard Error 1.33 |
Comparison: A5 minus T80/A5p-value: <0.00195% CI: [2.2807, 6.695]ANCOVA
Secondary
Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG.
Clinically relevant abnormalities for Physical examination, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time frame: From drug administration until end of treatment plus one day
Population: Treated set included patients who were randomised and took at least one dose of the trial medication in the double-blind treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Alanine aminotransferase increased | 0 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood glucose increased | 1 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood creatinine phosphokinase increased | 1 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Myocardial ischaemia | 1 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood creatinine increased | 0 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood glucose abnormal | 1 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Protein urine present | 2 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Heart rate increased | 0 participants |
| A5 Alone | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Atrial fibrilation | 0 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Heart rate increased | 1 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Atrial fibrilation | 1 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Myocardial ischaemia | 0 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood glucose increased | 4 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Protein urine present | 1 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Alanine aminotransferase increased | 1 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood creatinine phosphokinase increased | 0 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood glucose abnormal | 1 participants |
| T80/A5 | Clinically Relevant Abnormalities for Physical Examination, Pulse Rate, Laboratory Parameters and ECG. | Blood creatinine increased | 1 participants |
Secondary
DBP and SBP Control and Response After 4 Weeks of Treatment
DBP control is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment. SBP control is defined as SBP \<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment. DBP response is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=10mmHg. SBP response is defined as SBP\<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=15mmHg.
Time frame: Baseline and 4 weeks
Population: FAS with LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A5 Alone | DBP and SBP Control and Response After 4 Weeks of Treatment | DBP control | 71 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 4 Weeks of Treatment | SBP control | 91 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 4 Weeks of Treatment | DBP response | 87 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 4 Weeks of Treatment | SBP response | 108 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 4 Weeks of Treatment | SBP response | 124 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 4 Weeks of Treatment | DBP control | 95 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 4 Weeks of Treatment | DBP response | 108 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 4 Weeks of Treatment | SBP control | 103 Number of participants |
Secondary
DBP and SBP Control and Response After 8 Weeks of Treatment
DBP control is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment. SBP control is defined as SBP \<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment. DBP response is defined as DBP \<90 mmHg or \<80 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=10mmHg. SBP response is defined as SBP\<140 mmHg or \<130 mmHg in patients with diabetes or renal impairment or a reduction from baseline \>=15mmHg.
Time frame: Baseline and 8 weeks
Population: FAS with LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A5 Alone | DBP and SBP Control and Response After 8 Weeks of Treatment | DBP control | 85 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 8 Weeks of Treatment | SBP control | 100 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 8 Weeks of Treatment | DBP response | 101 Number of participants |
| A5 Alone | DBP and SBP Control and Response After 8 Weeks of Treatment | SBP response | 120 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 8 Weeks of Treatment | SBP response | 131 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 8 Weeks of Treatment | DBP control | 112 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 8 Weeks of Treatment | DBP response | 124 Number of participants |
| T80/A5 | DBP and SBP Control and Response After 8 Weeks of Treatment | SBP control | 119 Number of participants |
Secondary
Number of Patients in Blood Pressure Categories at 4 Weeks
BP optimal: SBP \<120 mmHg and DBP \<80 mmHg, BP normal: SBP \<130 mmHg and DBP \<85 mmHg but not optimal, BP high-normal: SBP \<140 mmHg and DBP \<90 mmHg but not normal. Grade 1 hypertension: SBP \<160 mmHg and DBP \<100 mmHg but not high-normal, Grade 2 hypertension: SBP \<180 mmHg and DBP \<110 mmHg but not grade 1, Grade 3 hypertension: SBP \>=180 mmHg or DBP \>=110 mmHg.
Time frame: 4 weeks
Population: FAS with LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | BP optimal | 1 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | BP normal | 20 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | BP high-normal | 35 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 1 hypertension | 81 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 2 hypertension | 17 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 3 hypertension | 5 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 2 hypertension | 15 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | BP optimal | 7 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 1 hypertension | 62 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | BP normal | 26 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | Grade 3 hypertension | 1 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories at 4 Weeks | BP high-normal | 44 Number of participants |
Secondary
Number of Patients in Blood Pressure Categories Over Time
BP optimal: SBP \<120 mmHg and DBP \<80 mmHg, BP normal: SBP \<130 mmHg and DBP \<85 mmHg but not optimal, BP high-normal: SBP \<140 mmHg and DBP \<90 mmHg but not normal. Grade 1 hypertension: SBP \<160 mmHg and DBP \<100 mmHg but not high-normal, Grade 2 hypertension: SBP \<180 mmHg and DBP \<110 mmHg but not grade 1, Grade 3 hypertension: SBP \>=180 mmHg or DBP \>=110 mmHg.
Time frame: 8 weeks
Population: FAS with LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | BP optimal | 7 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | BP normal | 33 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | BP high-normal | 32 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | Grade 1 hypertension | 69 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | Grade 2 hypertension | 15 Number of participants |
| A5 Alone | Number of Patients in Blood Pressure Categories Over Time | Grade 3 hypertension | 3 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | Grade 2 hypertension | 5 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | BP optimal | 11 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | Grade 1 hypertension | 48 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | BP normal | 36 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | Grade 3 hypertension | 2 Number of participants |
| T80/A5 | Number of Patients in Blood Pressure Categories Over Time | BP high-normal | 53 Number of participants |