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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L50/H12.5/A5 | Experimental | 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. |
|
| L50 + A5 | Active Comparator | Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E) | Drug | One tablet, containing 50 mg losartan potassium, 12.5 mg hydrochlorothiazide, and 5 mg amlodipine besylate, orally, once daily, for 8 weeks. |
| 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. |
| 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 |
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Inclusion criteria
Exclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25271811 | Result | Rakugi H, Tsuchihashi T, Shimada K, Numaguchi H, Nishida C, Yamaguchi H, Shirakawa M, Azuma K, Fujita KP. Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clin Exp Hypertens. 2015;37(3):260-6. doi: 10.3109/10641963.2014.954712. Epub 2014 Oct 1. | |
| 25716649 |
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All participants received single-blind losartan 50 mg (L50) + amlodipine 5 mg (A5) and placebo for L50/(H12.5)/A5 during 8-week Filter/Screening Period. A total of 707 entered the Filter/Screening Period and 327 were randomly assigned to 1 of the 2 treatment arms for the Double-blind Treatment Period.
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| ID | Title | Description |
|---|---|---|
| FG000 | L50/H12.5/A5 | 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. |
| FG001 | L50 + A5 | Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | L50/H12.5/A5 | 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. |
| BG001 | L50 + A5 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All participants that received at least one dose of study treatment, had at least 1 post-randomization observation for the analysis endpoint, and had baseline data | Posted | Least Squares Mean | 95% Confidence Interval | mmHg | Baseline and Week 8 |
|
up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L50/H12.5/A5 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sudden cardiac death | General disorders | MedDRA version 14.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA version 14.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck, Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| D000075222 | Essential Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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Not provided
| ID | Term |
|---|---|
| D019808 | Losartan |
| D006852 | Hydrochlorothiazide |
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Losartan potassium | Drug | One tablet, containing 50 mg losartan potassium, orally, once daily, for 8 weeks. |
|
| Amlodipine besylate | Drug | One capsule, containing 5 mg amlodipine besylate, orally, once daily, for 8 weeks. |
|
| Placebo to MK-0954E | Drug | One tablet, containing placebo, orally, once daily, for 8 weeks. |
|
| Placebo to losartan potassium | Drug | One tablet, containing placebo, orally, once daily, for 8 weeks. |
|
| Placebo to amlodipine besylate | Drug | One capsule, containing placebo, orally, once daily, for 8 weeks. |
|
| 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 |
| Result |
| Rakugi H, Tsuchihashi T, Shimada K, Numaguchi H, Nishida C, Yamaguchi H, Shirakawa M, Azuma K, Fujita KP. Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg. Hypertens Res. 2015 May;38(5):329-35. doi: 10.1038/hr.2015.3. Epub 2015 Feb 26. |
| Lost to Follow-up |
|
| Blood Pressure/Potassium Criteria Met |
|
| Physician Decision |
|
| Protocol Violation |
|
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| L50 + A5 |
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. |
|
|
|
| Primary | 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. | All randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | up to 14 days after last dose of study drug (up to 10 weeks) |
|
|
|
| Primary | 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. | All randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | up to 14 days after last dose of study drug (up to 10 weeks) |
|
|
|
| Primary | 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. | All randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | up to 14 days after last dose of study drug (up to 10 weeks) |
|
|
|
| Primary | 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 | All randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | up to 14 days after last dose of study drug (up to 10 weeks) |
|
|
|
| Primary | 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 | All randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | up to 8 weeks |
|
|
|
| Secondary | 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. | All participants that received at least one dose of study treatment, had at least 1 post-randomization observation for the analysis endpoint, and had baseline data | Posted | Least Squares Mean | 95% Confidence Interval | mmHg | Baseline and Week 8 |
|
|
|
|
| 1 |
| 164 |
| 11 |
| 164 |
| EG001 | L50 + A5 | Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks. | 1 | 163 | 15 | 163 |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA version 14.1 | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA version 14.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |