Hypertension
Conditions
Keywords
Hypertension, Uncontrolled hypertension, High blood pressure, Uncontrolled high blood pressure, Untreated high blood pressure, Untreated hypertension, Essential hypertension
Brief summary
This study will determine whether using losartan and amlodipine together will be non-inferior in lowering blood pressure than amlodipine alone.
Interventions
DRUGLosartan (+) amlodipine
One tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks.
DRUGPlacebo to match losartan/amlodipine tablets
One tablet containing placebo, orally, once daily, for 8 weeks.
DRUGAmlodipine camsylate
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks.
DRUGPlacebo to match amlodipine
2 tablets containing placebo, orally, once daily, for 8 weeks.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants with essential hypertension: * who are on single drug therapy * who are newly diagnosed and not yet taking any drug therapy, or have not had any drug therapy for at least 2 weeks prior to entering study * who have blood pressure readings of 90mmHg ≤ MSDBP \< 110mmHg and 140mmHg ≤ MSSBP \<180mmHg after 2 weeks wash-out for patients on single agent. * Randomization (Visit 3) * After dosing of amlodipine 5mg for 6 weeks, blood pressure readings are: * 90mmHg ≤ MSDBP \< 110mmHg and 140mmHg ≤ MSSBP \< 180mmHg.
Exclusion criteria
* Participant with MSDBP ≥ 110mmHg or MSSBP ≥ 180mmHg. * Participant currently taking ≥ 2 antihypertensive medications (note: fixed-dose combination medicine should be counted as the number of active ingredients). * Participant with known secondary hypertension of any etiology. * Participant with malignant hypertension or current evidence of impending or active malignant hypertension, including headache, papilledema, cardiac ischemia, or pulmonary congestion precipitated by elevated blood pressure. * Participant with known intolerance, contraindication or hypersensitivity to any component of dihydropyridines, angiotensin II receptor blockers. * Participant showing positive in pregnancy test, lactating woman, or woman who intends to get pregnant during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | Baseline and Week 8 | Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | Baseline and Week 8 | Systolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded. |
| Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4 | Baseline and Week 4 | Systolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded. |
| Percentage of Participants Who Achieve Target Blood Pressure at Week 8 | Week 8 | Participants were evaluated at Week 8 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline. |
| Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4 | Baseline and Week 4 | Diastolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded. |
| Percentage of Participants Who Had Peripheral Edema During the Study | up to 8 weeks | A pitting assessment of edema on both legs was performed at baseline and throughout the study. Participants were assessed in a seated position with both feet extended and the right ankle in a neutral dorsiflexion position. The index finger was pressed firmly over the bony prominence approximately 3cm proximal to the midpoint of the medial malleolus of the right ankle and will be held for three seconds. Presence of a residual indentation in the area after releasing pressure on the index finger was considered positive for pitting edema. |
| Change From Baseline in Ankle Circumference at Week 8 | Baseline and Week 8 | Each ankle was marked with a semi-permanent marker at approximately 3 cm proximal to the midpoint of the medial malleolus to aid consistency in the performance of the measurements. Ankle circumference was measured in both ankles at baseline and Week 8 using a tension controlled tape to minimize error. |
| Percentage of Participants Who Achieve Target Blood Pressure at Week 4 | Week 4 | Participants were evaluated at Week 4 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan/Amlodipine One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks. | 168 |
| Amlodipine 2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks. | 166 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Contraindicated medication used | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Participant moved | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 |
Baseline characteristics
| Characteristic | Losartan/Amlodipine | Amlodipine | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 10.5 | 51.8 years STANDARD_DEVIATION 10.6 | 52.9 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 42 Participants | 36 Participants | 78 Participants |
| Sex: Female, Male Male | 126 Participants | 130 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 168 | 11 / 166 |
| serious Total, serious adverse events | 6 / 168 | 5 / 166 |
Outcome results
Primary
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Time frame: Baseline and Week 8
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | -10.1 mmHg | Standard Deviation 7.6 |
| Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 | -8.8 mmHg | Standard Deviation 7.8 |
p-value: 0.133995% CI: [-3, 0.4]t-test, 2 sided
Secondary
Change From Baseline in Ankle Circumference at Week 8
Each ankle was marked with a semi-permanent marker at approximately 3 cm proximal to the midpoint of the medial malleolus to aid consistency in the performance of the measurements. Ankle circumference was measured in both ankles at baseline and Week 8 using a tension controlled tape to minimize error.
Time frame: Baseline and Week 8
Population: All participants who received at least 1 dose of study drug and had available data for ankle circumference.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losartan/Amlodipine | Change From Baseline in Ankle Circumference at Week 8 | Left Ankle | -0.6 mm | Standard Deviation 4.7 |
| Losartan/Amlodipine | Change From Baseline in Ankle Circumference at Week 8 | Right Ankle | -0.5 mm | Standard Deviation 4 |
| Amlodipine | Change From Baseline in Ankle Circumference at Week 8 | Left Ankle | -0.7 mm | Standard Deviation 4.4 |
| Amlodipine | Change From Baseline in Ankle Circumference at Week 8 | Right Ankle | -0.2 mm | Standard Deviation 4.2 |
p-value: 0.7911t-test, 2 sided
p-value: 0.5933t-test, 2 sided
Secondary
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4
Diastolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Time frame: Baseline and Week 4
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4 | -9.3 mmHg | Standard Deviation 7.8 |
| Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4 | -10.0 mmHg | Standard Deviation 7.9 |
p-value: 0.4478t-test, 2 sided
Secondary
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4
Systolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Time frame: Baseline and Week 4
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4 | -12.5 mmHg | Standard Deviation 13.2 |
| Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4 | -12.3 mmHg | Standard Deviation 10.9 |
p-value: 0.8736t-test, 2 sided
Secondary
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
Systolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Time frame: Baseline and Week 8
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | -15.0 mmHg | Standard Deviation 12.1 |
| Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 | -12.7 mmHg | Standard Deviation 10.7 |
p-value: 0.0717t-test, 2 sided
Secondary
Percentage of Participants Who Achieve Target Blood Pressure at Week 4
Participants were evaluated at Week 4 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.
Time frame: Week 4
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan/Amlodipine | Percentage of Participants Who Achieve Target Blood Pressure at Week 4 | 55.1 Percentage of Participants |
| Amlodipine | Percentage of Participants Who Achieve Target Blood Pressure at Week 4 | 61.5 Percentage of Participants |
p-value: 0.2508Chi-squared
Secondary
Percentage of Participants Who Achieve Target Blood Pressure at Week 8
Participants were evaluated at Week 8 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.
Time frame: Week 8
Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan/Amlodipine | Percentage of Participants Who Achieve Target Blood Pressure at Week 8 | 63.0 Percentage of Participants |
| Amlodipine | Percentage of Participants Who Achieve Target Blood Pressure at Week 8 | 58.8 Percentage of Participants |
p-value: 0.2508Chi-squared
Secondary
Percentage of Participants Who Had Peripheral Edema During the Study
A pitting assessment of edema on both legs was performed at baseline and throughout the study. Participants were assessed in a seated position with both feet extended and the right ankle in a neutral dorsiflexion position. The index finger was pressed firmly over the bony prominence approximately 3cm proximal to the midpoint of the medial malleolus of the right ankle and will be held for three seconds. Presence of a residual indentation in the area after releasing pressure on the index finger was considered positive for pitting edema.
Time frame: up to 8 weeks
Population: Safety Set defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan/Amlodipine | Percentage of Participants Who Had Peripheral Edema During the Study | 6.5 Percentage of Participants |
| Amlodipine | Percentage of Participants Who Had Peripheral Edema During the Study | 5.4 Percentage of Participants |
p-value: 0.6646Chi-squared