Hypertension
Conditions
Brief summary
The changes in the trough systolic blood pressure from the baseline were assessed after 8 weeks of double-blind treatment with amlodipine 10 mg or amlodipine 5 mg
Interventions
DRUGAmlodipine
Amlodipine 5mg/ day
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Untreated Hypertensive Patients: An systolic blood pressure of \>=160 mmHg or diastolic blood pressure \>=100mmHg. * Treated Hypertensive Patients: An systolic blood pressure of \>=140 mmHg or diastolic blood pressure of \>= 90 mmHg. * Patients with insufficient response to 5 mg of amlodipine in the screening period:Two successive systolic blood pressure measurements at Visit 4 (Week -2) and Visit 5 (Week 0 = baseline) \>=140 mmHg * Patients with a screening treatment compliance rate \>= 80%
Exclusion criteria
* Subjects with secondary hypertension (renal disease, pheochromocytoma, and Cushing's syndrome, etc.), severe hypertension (systolic blood pressure of 180 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher), and malignant hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 8 | Baseline to Week 8 | Mean change in the trough SBP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Mean Change in SBP From Baseline to Week 6 and Week 8 (Mean by Patient) | Baseline to Week 6 and Week 8 | Arithmetic mean of Week 6 & Week 8 by patient for Change from baseline in SBP at Week 6 and Change from baseline in SBP at Week 8 |
| Combined Mean Change in DBP From Baseline to Week 6 and Week 8 (Mean by Patient) | Baseline to Week 6 and Week 8 | Arithmetic mean of Week 6 & Week 8 by patient for Change from baseline in DBP at Week 6 and Change from baseline in DBP at Week 8 |
| Number of Subjects Achieving the Target Blood Pressure Reduction Value at Week 8 | Week 8 | Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old |
| Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value at Both Weeks 6 and 8 | Week 6 and Week 8 | Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old |
| Change in Diastolic Blood Pressure (DBP) From Baseline to Week 8 | Baseline to Week 8 | Mean change in the trough DBP |
| Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Both Weeks 6 and 8 | Week 6 and Week 8 | Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old |
| Trough Plasma Concentrations of Amlodipine -Amlodipine 5 mg | Baseline, Week 4 and Week 8 | — |
| Trough Plasma Concentrations of Amlodipine -Amlodipine 10 mg | Baseline, Week 4, and Week 8 | — |
| Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Week 8 | Week 8 | Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old |
Countries
Japan
Participant flow
Recruitment details
Twenty-four (24) centers in Japan
Pre-assignment details
Consent was taken from 414 patients, 356 patients who met the screening criteria received amlodipine 5 mg. After the 8 weeks of screening treatment, patients who met the entry criteria for double-blind period were randomized to either the amlodipine 10 mg group or the amlodipine 5 mg group at a ratio of 1:1.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine 5 mg One amlodipine besilate 5 mg tablet and 1 amlodipine besilate 5 mg placebo tablet were administered once daily after breakfast for 8 weeks. | 154 |
| Amlodipine 10 mg Two amlodipine besilate 5 mg tablets were administered once daily after breakfast for 8 weeks. | 151 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Amlodipine 5 mg | Amlodipine 10 mg |
|---|---|---|---|
| Age, Customized 20 to 44 years | 30 partcipants | 15 partcipants | 15 partcipants |
| Age, Customized < 20 years | 0 partcipants | 0 partcipants | 0 partcipants |
| Age, Customized 45 to 64 years | 145 partcipants | 75 partcipants | 70 partcipants |
| Age, Customized >= 65 years | 130 partcipants | 64 partcipants | 66 partcipants |
| Region of Enrollment Japan | 305 participants | 154 participants | 151 participants |
| Sex: Female, Male Female | 129 Participants | 70 Participants | 59 Participants |
| Sex: Female, Male Male | 176 Participants | 84 Participants | 92 Participants |
Outcome results
Primary
Change in Systolic Blood Pressure (SBP) From Baseline to Week 8
Mean change in the trough SBP
Time frame: Baseline to Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 8 | -7.0 mmHg |
| Amlodipine 10 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 8 | -13.7 mmHg |
Comparison: The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). ANCOVA models with the trough SBP at baseline, body weight, and age as covariates, and the treatment group and study site as factors was used. The test was performed with a significance level of 0.05 (two-sided).p-value: <0.00195% CI: [-9, -4.4]ANCOVA
Secondary
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 8
Mean change in the trough DBP
Time frame: Baseline to Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Change in Diastolic Blood Pressure (DBP) From Baseline to Week 8 | -2.7 mmHg |
| Amlodipine 10 mg | Change in Diastolic Blood Pressure (DBP) From Baseline to Week 8 | -6.8 mmHg |
Comparison: The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). ANCOVA models with the trough DBP at baseline, body weight, and age as covariates, and the treatment group and study site as factors was used. The test was performed with a significance level of 0.05 (two-sided).p-value: <0.00195% CI: [-5.7, -2.5]ANCOVA
Secondary
Combined Mean Change in DBP From Baseline to Week 6 and Week 8 (Mean by Patient)
Arithmetic mean of Week 6 & Week 8 by patient for Change from baseline in DBP at Week 6 and Change from baseline in DBP at Week 8
Time frame: Baseline to Week 6 and Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Combined Mean Change in DBP From Baseline to Week 6 and Week 8 (Mean by Patient) | -2.5 mmHg |
| Amlodipine 10 mg | Combined Mean Change in DBP From Baseline to Week 6 and Week 8 (Mean by Patient) | -6.5 mmHg |
Comparison: The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). ANCOVA models with the trough DBP at baseline, body weight, and age as covariates, and the treatment group and study site as factors was used. The test was performed with a significance level of 0.05 (two-sided).p-value: <0.00195% CI: [-5.4, -2.6]ANCOVA
Secondary
Combined Mean Change in SBP From Baseline to Week 6 and Week 8 (Mean by Patient)
Arithmetic mean of Week 6 & Week 8 by patient for Change from baseline in SBP at Week 6 and Change from baseline in SBP at Week 8
Time frame: Baseline to Week 6 and Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Combined Mean Change in SBP From Baseline to Week 6 and Week 8 (Mean by Patient) | -6.8 mmHg |
| Amlodipine 10 mg | Combined Mean Change in SBP From Baseline to Week 6 and Week 8 (Mean by Patient) | -13.9 mmHg |
Comparison: The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). ANCOVA models with the trough SBP at baseline, body weight, and age as covariates, and the treatment group and study site as factors was used. The test was performed with a significance level of 0.05 (two-sided).p-value: <0.00195% CI: [-9.1, -5.1]ANCOVA
Secondary
Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Both Weeks 6 and 8
Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old
Time frame: Week 6 and Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 5 mg | Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Both Weeks 6 and 8 | 16 participants |
| Amlodipine 10 mg | Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Both Weeks 6 and 8 | 44 participants |
Comparison: Proportions of participants (responder rates) were used for the statistical analyses. The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). The test was conducted based on a logistic regression model with baseline SBP value and body weight as covariates, and treatment group and age (\<=64, \>=65) as a factor. The significance level was 0.05 (two-sided).p-value: <0.00195% CI: [2.12, 8.19]Regression, Logistic
Secondary
Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value at Both Weeks 6 and 8
Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old
Time frame: Week 6 and Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 5 mg | Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value at Both Weeks 6 and 8 | 22 participants |
| Amlodipine 10 mg | Combined Number of Subjects Achieving the Target Blood Pressure Reduction Value at Both Weeks 6 and 8 | 52 participants |
Comparison: Proportions of participants (responder rates) were used for the statistical analyses. The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). The test was conducted based on a logistic regression model with baseline SBP value and body weight as covariates, and treatment group and age (\<=64, \>=65) as a factor. The significance level was 0.05 (two-sided).p-value: <0.00195% CI: [2.28, 8.74]Regression, Logistic
Secondary
Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Week 8
Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old
Time frame: Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 5 mg | Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Week 8 | 35 participants |
| Amlodipine 10 mg | Number of Subjects Achieving the Target Blood Pressure Reduction Value and Whose SBP Decreased From Baseline by >= 10 mmHg at Week 8 | 61 participants |
Comparison: Proportions of participants (responder rates) were used for the statistical analyses. The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). The test was conducted based on a logistic regression model with baseline SBP value and body weight as covariates, and treatment group and age (\<=64, \>=65) as a factor. The significance level was 0.05 (two-sided).p-value: 0.00195% CI: [1.5, 4.36]Regression, Logistic
Secondary
Number of Subjects Achieving the Target Blood Pressure Reduction Value at Week 8
Target blood pressure reduction value based on Japan Society of Hypertension Guidelines for the Management of Hypertension 2004: SBP below 130 mmHg and DBP below 85 mmHg for \<=64 years old; SBP below 140 mmHg and DBP below 90 mmHg for \>=65 years old
Time frame: Week 8
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 5 mg | Number of Subjects Achieving the Target Blood Pressure Reduction Value at Week 8 | 43 participants |
| Amlodipine 10 mg | Number of Subjects Achieving the Target Blood Pressure Reduction Value at Week 8 | 66 participants |
Comparison: Proportions of participants (responder rates) were used for the statistical analyses. The hypothesis of no group differences (null hypothesis) was tested against that of the amlodipine 10 mg arm being superior to the amlodipine 5 mg arm (alternative hypothesis). The test was conducted based on a logistic regression model with baseline SBP value and body weight as covariates, and treatment group and age (\<=64, \>=65) as a factor. The significance level was 0.05 (two-sided).p-value: 0.00295% CI: [1.36, 3.99]Regression, Logistic
Secondary
Trough Plasma Concentrations of Amlodipine -Amlodipine 10 mg
Time frame: Baseline, Week 4, and Week 8
Population: Plasma concentration obtained after temporarily dosing discontinuation or not matched with the following conditions were excluded from the analysis; Steady-state condition: at least 80% drug compliance from the previous visit to the day of sampling; Trough condition: samples taken within ±10% of 24 hours from last dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Trough Plasma Concentrations of Amlodipine -Amlodipine 10 mg | 7.18 ng/mL |
| Amlodipine 10 mg | Trough Plasma Concentrations of Amlodipine -Amlodipine 10 mg | 16.9 ng/mL |
| Week 8 | Trough Plasma Concentrations of Amlodipine -Amlodipine 10 mg | 16.9 ng/mL |
Secondary
Trough Plasma Concentrations of Amlodipine -Amlodipine 5 mg
Time frame: Baseline, Week 4 and Week 8
Population: Plasma concentration obtained after temporarily dosing discontinuation or not matched with the following conditions were excluded from the analysis; Steady-state condition: at least 80% drug compliance from the previous visit to the day of sampling; Trough condition: samples taken within ±10% of 24 hours from last dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Amlodipine 5 mg | Trough Plasma Concentrations of Amlodipine -Amlodipine 5 mg | 7.02 ng/mL |
| Amlodipine 10 mg | Trough Plasma Concentrations of Amlodipine -Amlodipine 5 mg | 6.83 ng/mL |
| Week 8 | Trough Plasma Concentrations of Amlodipine -Amlodipine 5 mg | 7.03 ng/mL |