Hypertension
Conditions
Keywords
Essential hypertension, Uncontrolled hypertension, Antihypertensive agents, Blood pressure
Brief summary
This study is being conducted to evaluate the safety of MK-0954A (L100/H12.5 mg) in essential hypertension participants who are uncontrolled with MK-954H (L50/H12.5 mg).
Interventions
DRUGMK-0954A
Tablet containing losartan potassium (100 mg) and hydrochlorothiazide (12.5 mg), once daily
DRUGMK-954H
Tablet containing losartan potassium (50 mg) and hydrochlorothiazide (12.5 mg), once daily
Placebo tablet to match MK-0954A, once daily
DRUGPlacebo to MK-954H
Placebo tablet to match MK-954H, 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 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 \>=90mmHg and \< 110mmHg. * Participant has a mean trough SiSBP of \>=140mmHg and \< 200mmHg. * 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 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. * 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 |
|---|---|
| Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension) | Up to 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | Baseline and Week 8 (End of Double-blind Period) | Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings. |
| Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | Baseline and Week 8 (End of Double-blind Period) | Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0954H (L50/H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will then receive open label MK-0954A (L100/H12.5) orally, once daily for 44 weeks (extension) | 144 |
| MK-0954A (L100/H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will continue to receive MK-0954A orally, once daily for 44 week extension. | 134 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 44-week Open-label Extension | Adverse Event | 0 | 0 | 2 | 1 |
| 44-week Open-label Extension | Blood Pressure Withdrawal Criteria Met | 0 | 0 | 0 | 2 |
| 44-week Open-label Extension | Death | 0 | 0 | 0 | 1 |
| 44-week Open-label Extension | Physician Decision | 0 | 0 | 1 | 0 |
| 44-week Open-label Extension | Potassium Withdrawal Criteria Met | 0 | 0 | 6 | 7 |
| 44-week Open-label Extension | Withdrawal by Subject | 0 | 0 | 2 | 1 |
| 8-week Double-blind Period | Adverse Event | 2 | 0 | 0 | 0 |
| 8-week Double-blind Period | Blood Pressure Withdrawal Criteria Met | 0 | 3 | 0 | 0 |
| 8-week Double-blind Period | Lack of Efficacy | 1 | 0 | 0 | 0 |
| 8-week Double-blind Period | Potassium Withdrawal Criteria Met | 6 | 3 | 0 | 0 |
| 8-week Double-blind Period | Withdrawal by Subject | 4 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-0954H (L50/H12.5) | MK-0954A (L100/H12.5) | Total |
|---|---|---|---|
| Age, Continuous | 56.9 Years STANDARD_DEVIATION 10.7 | 57.8 Years STANDARD_DEVIATION 10.8 | 57.3 Years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 41 Participants | 32 Participants | 73 Participants |
| Sex: Female, Male Male | 103 Participants | 102 Participants | 205 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 / 144 | 20 / 134 | 47 / 131 | 43 / 127 |
| serious Total, serious adverse events | 1 / 144 | 2 / 134 | 6 / 131 | 1 / 127 |
Outcome results
Primary
Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension)
Time frame: Up to 52 weeks
Population: All-Patients-as-Treated (APaT) Population, which consists of all randomized patients who received at least one dose of MK-0954A. The L100/H12.5 (L50/H12.5) arm only includes data from extension period (44 weeks); L100/H12.5→L100/H12.5 Open Label arm includes data from entire study period (52 weeks).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0954H (L50/H12.5) | Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension) | 71.0 Percentage of Participants |
| MK-0954A (L100/H12.5) | Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension) | 72.4 Percentage of Participants |
Secondary
Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8
Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings.
Time frame: Baseline and Week 8 (End of Double-blind Period)
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-0954H (L50/H12.5) | Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | -5.3 mmHg | 95% Confidence Interval 0.7 |
| MK-0954A (L100/H12.5) | Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | -5.0 mmHg | 95% Confidence Interval 0.7 |
95% CI: [-1.7, 2.2]Constained logitudinal data analysis
Secondary
Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8
Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings.
Time frame: Baseline and Week 8 (End of Double-blind Period)
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-0954H (L50/H12.5) | Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | -6.2 mmHg |
| MK-0954A (L100/H12.5) | Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | -8.5 mmHg |
95% CI: [-5, 0.5]Constained longitudinal data analysis