Hypertension
Conditions
Keywords
Essential hypertension, Uncontrolled hypertension, Antihypertensive agents, Blood pressure
Brief summary
This study is being conducted to evaluate the efficacy of MK-0954A in essential hypertension participants who are not adequately controlled with losartan.
Interventions
DRUGMK-0954A
Tablet containing losartan potassium (100 mg) and hydrochlorothiazide (12.5 mg), once daily
DRUGLosartan
Tablet containing losartan potassium (100 mg), once daily
Placebo tablet to match MK-0954A, once daily
DRUGPlacebo to losartan 100 mg
Placebo tablet to match losartan 100 mg, once daily
DRUGPlacebo to losartan 50 mg
Placebo tablet to match losartan 50 mg, once daily
Sponsors
Organon and Co
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 not treated with antihypertensive medication and meets protocol-specified blood pressure criteria. * Participant is treated with single antihypertensive medication, and meets protocol-specified blood pressure criteria. * Participant is being treated with up to dual oral antihypertensive medications, and will be able to discontinue the prior antihypertensive medication. * Participant has no clinically meaningful findings to be disqualified from the study at the discretion of the investigator.
Exclusion criteria
* Regarding hypertension, 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 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 a recent history within the last year of drug or alcohol abuse or dependence. * Participant is pregnant or breastfeeding or expecting to conceive or has a positive pregnancy test at the screening visit. * Participant is currently participating or has participated in a study with an investigational compound (except losartan at any doses) or device within 30 days of signing informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) | 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 (Day 56 ± 7 days). |
| Percentage of Participants Who Experienced at Least One Adverse Event (AE) | 8 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) | 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 (Day 56 ± 7 days). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0954A Participants administered MK-0954A, Placebo for Losartan 50 mg , and Placebo for Losartan 100 mg orally, once daily for 8 weeks. | 166 |
| Losartan Participants administered Losartan 100 mg, Placebo for MK-0954A, and Placebo for Losartan 50 mg orally, once daily for 8 weeks. | 170 |
| Total | 336 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Blood Pressure Withdrawal Criteria Met | 2 | 3 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Serum Potassium Withdrawal Criteria Met | 4 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | MK-0954A | Losartan | Total |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 9.2 | 54.9 years STANDARD_DEVIATION 9.5 | 55.3 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 37 Participants | 60 Participants | 97 Participants |
| Sex: Female, Male Male | 129 Participants | 110 Participants | 239 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 166 | 9 / 170 |
| serious Total, serious adverse events | 0 / 166 | 0 / 170 |
Outcome results
Primary
Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP)
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 (Day 56 ± 7 days).
Time frame: Baseline and Week 8
Population: Full Analysis Set (FAS) population: defined as all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent~to at least one dose of study treatment, and had baseline data for those analyses that required baseline data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK-0954A | Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) | -8.7 mmHg | 95% Confidence Interval 0.6 |
| Losartan | Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) | -3.6 mmHg | 95% Confidence Interval 0.6 |
p-value: <0.00195% CI: [-6.8, -3.4]constrained longitudinal data analysis
Primary
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
Time frame: 8 weeks
Population: All-Patients-as-Treated (APaT) Population: defined as all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0954A | Percentage of Participants Who Experienced at Least One Adverse Event (AE) | 31.3 percentage of participants |
| Losartan | Percentage of Participants Who Experienced at Least One Adverse Event (AE) | 26.5 percentage of participants |
Secondary
Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP)
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 (Day 56 ± 7 days).
Time frame: Baseline and Week 8
Population: Full Analysis Set (FAS) Population: defined as all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent~to at least one dose of study treatment, and had baseline data for those analyses that required baseline data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0954A | Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) | -14.5 mmHg |
| Losartan | Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) | -5.4 mmHg |
p-value: <0.00195% CI: [-11.9, -6.5]constrained longitudinal data analysis