Hypertension
Conditions
Keywords
Essential hypertension, Antihypertensive agents, Blood pressure, Uncontrolled hypertension
Brief summary
This study has two parts. In the first part, the efficacy and safety MK-0954E (losartan potassium 50 mg \[L50\] (+) hydrochlorothiazide 12.5 mg \[H12.5\] (+) amlodipine besylate 5mg \[A5\]) will be evaluated and compared to the efficacy and safety of MK-0954H (L50/H12.5) in Japanese participants. In the second part, the safety and tolerability of long-term use of open-label MK-0954E in participants with hypertension will be evaluated. The primary hypothesis is that MK-0954E is more effective in lowering mean trough sitting diastolic blood pressure (SiDBP) after 8 weeks of treatment compared to MK-954H (L50/H12.5 mg) in Japanese participants with essential hypertension who are not adequately controlled following a 8-week treatment with filter period study drug of MK-954H.
Interventions
DRUGL50/H12.5/A5
DRUGL50/H12.5
DRUGPlacebo to L50/H12.5/A5
DRUGPlacebo to L50/H12.5
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant has a diagnosis of essential hypertension * Participant is being treated with a single, or dual combination treatment for hypertension and will be able to discontinue the prior antihypertensive medication * Participant has a mean trough SiDBP of ≥ 90 mmHg and \< 110 mmHg * Participant has a mean trough SiSBP of ≥ 140 mmHg and \< 200 mmHg * Participant has no clinically significant abnormality at screening visit
Exclusion criteria
* Participant is currently taking \>2 antihypertensive medications * Participant has a history of significant multiple and/or severe allergies to ingredients of Nu-Lotan or Preminent, amlodipine or dihydropyridine drug and thiazide drug or related drug (i.e., sulfonamide-containing chlortalidone medicines) * Participant is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history within the last year of drug or alcohol abuse or dependence * Participant is pregnant or breastfeeding, or expecting to conceive OR the pregnancy test is positive at screening visit (Visit 1) * Participant is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term | Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug discontinued during the 44 week extension due to an AE regardless of completion status were summarized. |
| Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period | Baseline and Week 8 | Sitting diastolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. The difference between the baseline and Week 8 assessments was calculated and summarized by treatment arm. |
| Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period | up to Week 8 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced at least 1 AE during the 8-week double-blind treatment period were summarized by study drug received. |
| Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period | up to Week 8 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received. |
| Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period | up to Week 8 | An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The percentage of participants who experienced at least 1 SAE during the 8-week double-blind treatment period were summarized by study drug received. |
| Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period | up to Week 8 | An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Percentage of participants that experienced at least 1 SAE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received. |
| Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period | up to Week 8 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug stopped during the 8-week double-blind treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm. |
| Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term | Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants that experienced at least 1 AE during long-term period was summarized. |
| Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term | Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5 | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the long-term reporting period was summarized. |
| Percentage of Participants Who Experience 1 or More SAEs- Long Term | Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5 | An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Those SAEs assessed as possibly, probably, or definitely related to the study drug during the long-term period were summarized. |
| Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term | Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5 | An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. the percentage of participants that experienced an SAE that assessed as possibly, probably, or definitely related to the study drug by the investigator was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period | Baseline and Week 8 | Sitting systolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. |
Participant flow
Pre-assignment details
All participants received single-blind losartan 50 mg (L50)/hydrochlorothiazide 12.5 mg (H12.5) and placebo for L50/H12.5/amlodipine 5 mg (A5) during 8-week Filter Period. A total of 510 entered the Filter Period and 286 were randomly assigned to 1 of the 2 treatment arms for the Double-blind Treatment Period.
Participants by arm
| Arm | Count |
|---|---|
| L50/H12.5/A5→L50/H12.5/A5 One combination tablet containing L50 mg, H12.5 mg, and A5 mg, orally, once daily, for up to 8 weeks (double-blind treatment period). Participants continue with once daily L50/H12.5/A5 for 44 weeks during open-label extension. | 141 |
| L50/H12.5→L50/H12.5/A5 One combination tablet containing L50 mg and H12.5 mg, orally, once daily, for up to 8 weeks during double-blind treatment period. Participants then receive once daily L50/H12.5/A5 for 44 weeks during open-label extension. | 145 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment (Weeks 1 to 8) | Adverse Event | 1 | 2 |
| Double-blind Treatment (Weeks 1 to 8) | Blood Pressure/Potassium Criteria Met | 4 | 7 |
| Double-blind Treatment (Weeks 1 to 8) | Lack of Efficacy | 0 | 1 |
| Double-blind Treatment (Weeks 1 to 8) | Lost to Follow-up | 0 | 1 |
| Double-blind Treatment (Weeks 1 to 8) | Protocol Violation | 1 | 0 |
| Double-blind Treatment (Weeks 1 to 8) | Withdrawal by Subject | 1 | 1 |
| Extension (Weeks 9 to 52) | Adverse Event | 2 | 3 |
| Extension (Weeks 9 to 52) | Blood Pressure/Potassium Criteria Met | 4 | 9 |
| Extension (Weeks 9 to 52) | Lost to Follow-up | 1 | 2 |
| Extension (Weeks 9 to 52) | Physician Decision | 1 | 0 |
| Extension (Weeks 9 to 52) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | L50/H12.5/A5→L50/H12.5/A5 | L50/H12.5→L50/H12.5/A5 | Total |
|---|---|---|---|
| Age, Continuous | 53.9 Years STANDARD_DEVIATION 9.1 | 56.3 Years STANDARD_DEVIATION 9.7 | 55.1 Years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 33 Participants | 34 Participants | 67 Participants |
| Sex: Female, Male Male | 108 Participants | 111 Participants | 219 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 | 18 / 145 | 10 / 141 | 39 / 134 | 42 / 133 |
| serious Total, serious adverse events | 2 / 145 | 1 / 141 | 2 / 134 | 4 / 133 |
Outcome results
Primary
Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period
Sitting diastolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. The difference between the baseline and Week 8 assessments was calculated and summarized by treatment arm.
Time frame: Baseline and Week 8
Population: All participants that received at least one dose of study treatment during double-blind treatment period , had at least 1 post-randomization observation for the analysis endpoint, and had baseline data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| L50/H12.5/A5 | Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period | -12.1 mmHg |
| L50/H12.5 | Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period | -6.2 mmHg |
p-value: <0.00195% CI: [-7.5, -4.2]Contrained Longitudinal Data Analysis
Primary
Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced at least 1 AE during the 8-week double-blind treatment period were summarized by study drug received.
Time frame: up to Week 8
Population: All randomized participants who received at least 1 dose of study drug during double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period | 27.0 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period | 29.7 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants that experienced at least 1 AE during long-term period was summarized.
Time frame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Population: All randomized participants who received at least 1 dose of study drug during long-term reporting period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term | 70.9 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term | 66.2 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received.
Time frame: up to Week 8
Population: All randomized participants who received at least 1 dose of study drug during double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period | 12.1 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period | 14.5 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the long-term reporting period was summarized.
Time frame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Population: All randomized participants who received at least 1 dose of study drug during long-term reporting period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term | 27.7 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term | 14.3 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term
An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. the percentage of participants that experienced an SAE that assessed as possibly, probably, or definitely related to the study drug by the investigator was summarized.
Time frame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Population: All randomized participants who received at least 1 dose of study drug during long-term reporting period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term | 0.0 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term | 0.8 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period
An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Percentage of participants that experienced at least 1 SAE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received.
Time frame: up to Week 8
Population: All randomized participants who received at least 1 dose of study drug during double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period | 0.0 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or More SAEs- Long Term
An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Those SAEs assessed as possibly, probably, or definitely related to the study drug during the long-term period were summarized.
Time frame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Population: All randomized participants who received at least 1 dose of study drug during long-term reporting period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or More SAEs- Long Term | 2.1 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or More SAEs- Long Term | 3.0 Percentage of Participants |
Primary
Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period
An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The percentage of participants who experienced at least 1 SAE during the 8-week double-blind treatment period were summarized by study drug received.
Time frame: up to Week 8
Population: All randomized participants who received at least 1 dose of study drug during double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period | 0.7 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period | 1.4 Percentage of Participants |
Primary
Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug stopped during the 8-week double-blind treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm.
Time frame: up to Week 8
Population: All randomized participants who received at least 1 dose of study drug during double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period | 0.7 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period | 1.4 Percentage of Participants |
Primary
Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug discontinued during the 44 week extension due to an AE regardless of completion status were summarized.
Time frame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Population: All randomized participants who received at least 1 dose of study drug during extension period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L50/H12.5/A5 | Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term | 2.1 Percentage of Participants |
| L50/H12.5 | Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term | 2.3 Percentage of Participants |
Secondary
Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period
Sitting systolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8.
Time frame: Baseline and Week 8
Population: All participants that received at least one dose of study treatment during double-blind treatment period , had at least 1 post-randomization observation for the analysis endpoint, and had baseline data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| L50/H12.5/A5 | Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period | -17.7 mmHg |
| L50/H12.5 | Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period | -7.5 mmHg |
p-value: <0.00195% CI: [-12.8, -7.7]Constrained Longitudinal Data Analysis