MK-0954E Study in Participants With Hypertension (MK-0954E-357)

Study Overview
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Brief Summary
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This study is being done to evaluate the efficacy, safety, and tolerability of losartan potassium 50 mg (L50) + hydrochlorothiazide 12.5 mg (H12.5) + amlodipine besylate 5 mg (A5) (MK-0954E). The primary hypothesis is that L50/H12.5/A5 is more effective in lowering mean trough sitting diastolic blood pressure (SiDBP) after 8 weeks of treatment compared to L50+A5 in Japanese participants with essential hypertension who are not adequately controlled following an 8-week treatment with filter period study drug (L50+A5).

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 Losartan and Amlodipine Co-administration

Conditions
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Hypertension

Intervention / Treatment
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* Drug: losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E)
* Drug: Losartan potassium
* Drug: Amlodipine besylate
* Drug: Placebo to MK-0954E
* Drug: Placebo to losartan potassium
* Drug: Placebo to amlodipine besylate


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 single or dual 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<br>Participants receive 1 tablet, containing 50 mg losartan potassium (L50), 12.5 mg hydrochlorothiazide (H12.5), and 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. | Drug: losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E)<br>* One tablet, containing 50 mg losartan potassium, 12.5 mg hydrochlorothiazide, and 5 mg amlodipine besylate, orally, once daily, for 8 weeks.<br>Drug: Placebo to losartan potassium<br>* One tablet, containing placebo, orally, once daily, for 8 weeks.<br>Drug: Placebo to amlodipine besylate<br>* One capsule, containing placebo, orally, once daily, for 8 weeks.<br>|
| Active Comparator: L50 + A5<br>Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. | Drug: Losartan potassium<br>* One tablet, containing 50 mg losartan potassium, orally, once daily, for 8 weeks.<br>Drug: Amlodipine besylate<br>* One capsule, containing 5 mg amlodipine besylate, orally, once daily, for 8 weeks.<br>Drug: Placebo to MK-0954E<br>* One tablet, containing placebo, orally, once daily, for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean 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 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 Adverse Event (AE) | 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 10-week treatment and follow-up period were summarized by study drug received. | up to 14 days after last dose of study drug (up to 10 weeks) | 
| Percentage of Participants Who Experience ≥1 Drug-related AE | 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 10-week treatment and follow-up period were summarized by study drug received. | up to 14 days after last dose of study drug (up to 10 weeks) | 
| Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE) | 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 10-week treatment and follow-up period were summarized by study drug received. | up to 14 days after last dose of study drug (up to 10 weeks) | 
| Percentage of Participants Who Experience ≥1 Drug-related SAE | 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 10-week treatment and follow-up period were summarized by study drug received | up to 14 days after last dose of study drug (up to 10 weeks) | 
| Percentage of Participants Who Had Study Drug Stopped Due to an AE | 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 treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean 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 at Week 8. The difference between the baseline and Week 8 assessments was calculated and summarized by treatment arm. | 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, Uncontrolled hypertension, Antihypertensive agents, Blood pressure