MK-0954E Phase III Long-Term Study in Participants With Hypertension (MK-0954E-356)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Randomized, Active-Comparator Controlled Clinical Trial to Study the Efficacy and Safety of MK-0954E in Japanese Patients With Essential Hypertension Uncontrolled With MK-954H (L50/H12.5 mg) [PREMINENT®] and an Open-label, Long-term Clinical Trial to Study the Safety of MK-0954E

Conditions
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Hypertension

Intervention / Treatment
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* Drug: L50/H12.5/A5
* Drug: L50/H12.5
* Drug: Placebo to L50/H12.5/A5
* Drug: Placebo to L50/H12.5


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L50/H12.5/A5→L50/H12.5/A5<br>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. | Drug: L50/H12.5/A5<br> <br> * Other names: MK-0954E;Drug: Placebo to L50/H12.5<br> <br> |
| Active Comparator: L50/H12.5→L50/H12.5/A5<br>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 | Drug: L50/H12.5<br> <br> * Other names: MK-0954H;Drug: Placebo to L50/H12.5/A5<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 8 | 
| 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. | up to Week 8 | 
| 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. | up to Week 8 | 
| 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. | up to Week 8 | 
| 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. | up to Week 8 | 
| 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. | up to Week 8 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential hypertension, Antihypertensive agents, Blood pressure, Uncontrolled hypertension