MK-0954E Study in Participants With Hypertension (MK-0954E-357)
Primary Purpose
Hypertension
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E)
Losartan potassium
Amlodipine besylate
Placebo to MK-0954E
Placebo to losartan potassium
Placebo to amlodipine besylate
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Essential hypertension, Uncontrolled hypertension, Antihypertensive agents, Blood pressure
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
L50/H12.5/A5
L50 + A5
Arm Description
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.
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01302691
First Posted
February 22, 2011
Last Updated
February 28, 2019
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01302691
Brief Title
MK-0954E Study in Participants With Hypertension (MK-0954E-357)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 1, 2011 (Actual)
Primary Completion Date
April 1, 2012 (Actual)
Study Completion Date
April 1, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Essential hypertension, Uncontrolled hypertension, Antihypertensive agents, Blood pressure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
327 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L50/H12.5/A5
Arm Type
Experimental
Arm Description
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.
Arm Title
L50 + A5
Arm Type
Active Comparator
Arm Description
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E)
Intervention Description
One tablet, containing 50 mg losartan potassium, 12.5 mg hydrochlorothiazide, and 5 mg amlodipine besylate, orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Losartan potassium
Intervention Description
One tablet, containing 50 mg losartan potassium, orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Amlodipine besylate
Intervention Description
One capsule, containing 5 mg amlodipine besylate, orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo to MK-0954E
Intervention Description
One tablet, containing placebo, orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo to losartan potassium
Intervention Description
One tablet, containing placebo, orally, once daily, for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo to amlodipine besylate
Intervention Description
One capsule, containing placebo, orally, once daily, for 8 weeks.
Primary Outcome Measure Information:
Title
Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)
Description
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.
Time Frame
Baseline and Week 8
Title
Percentage of Participants Who Experience ≥1 Adverse Event (AE)
Description
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.
Time Frame
up to 14 days after last dose of study drug (up to 10 weeks)
Title
Percentage of Participants Who Experience ≥1 Drug-related AE
Description
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.
Time Frame
up to 14 days after last dose of study drug (up to 10 weeks)
Title
Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)
Description
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.
Time Frame
up to 14 days after last dose of study drug (up to 10 weeks)
Title
Percentage of Participants Who Experience ≥1 Drug-related SAE
Description
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
Time Frame
up to 14 days after last dose of study drug (up to 10 weeks)
Title
Percentage of Participants Who Had Study Drug Stopped Due to an AE
Description
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
Time Frame
up to 8 weeks
Secondary Outcome Measure Information:
Title
Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)
Description
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.
Time Frame
Baseline and Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25271811
Citation
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.
Results Reference
result
PubMed Identifier
25716649
Citation
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.
Results Reference
result
Learn more about this trial
MK-0954E Study in Participants With Hypertension (MK-0954E-357)
We'll reach out to this number within 24 hrs