search
Back to results

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

Primary Purpose

Hypertension

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
L50/H12.5/A5
L50/H12.5
Placebo to L50/H12.5/A5
Placebo to L50/H12.5
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Essential hypertension, Antihypertensive agents, Blood pressure, Uncontrolled hypertension

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    L50/H12.5/A5→L50/H12.5/A5

    L50/H12.5→L50/H12.5/A5

    Arm Description

    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.

    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

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    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.

    Full Information

    First Posted
    February 16, 2011
    Last Updated
    July 24, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT01299376
    Brief Title
    MK-0954E Phase III Long-Term Study in Participants With Hypertension (MK-0954E-356)
    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 MK-954H (L50/H12.5 mg) [PREMINENT®] and an Open-label, Long-term Clinical Trial to Study the Safety of MK-0954E
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    January 24, 2011 (Actual)
    Primary Completion Date
    November 16, 2011 (Actual)
    Study Completion Date
    September 20, 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 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypertension
    Keywords
    Essential hypertension, Antihypertensive agents, Blood pressure, Uncontrolled hypertension

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    286 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    L50/H12.5/A5→L50/H12.5/A5
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    L50/H12.5→L50/H12.5/A5
    Arm Type
    Active Comparator
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    L50/H12.5/A5
    Other Intervention Name(s)
    MK-0954E
    Intervention Type
    Drug
    Intervention Name(s)
    L50/H12.5
    Other Intervention Name(s)
    MK-0954H
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to L50/H12.5/A5
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to L50/H12.5
    Primary Outcome Measure Information:
    Title
    Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period
    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 or More Adverse Events (AEs)- Double-Blind Treatment Period
    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 8-week double-blind treatment period were summarized by study drug received.
    Time Frame
    up to Week 8
    Title
    Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period
    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 8-week double-blind treatment period were summarized by study drug received.
    Time Frame
    up to Week 8
    Title
    Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period
    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 8-week double-blind treatment period were summarized by study drug received.
    Time Frame
    up to Week 8
    Title
    Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period
    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 8-week double-blind treatment period were summarized by study drug received.
    Time Frame
    up to Week 8
    Title
    Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period
    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 double-blind treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm.
    Time Frame
    up to Week 8
    Title
    Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term
    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 that experienced at least 1 AE during long-term period was summarized.
    Time Frame
    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
    Title
    Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term
    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 long-term reporting period was summarized.
    Time Frame
    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
    Title
    Percentage of Participants Who Experience 1 or More SAEs- Long Term
    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. Those SAEs assessed as possibly, probably, or definitely related to the study drug during the long-term period were summarized.
    Time Frame
    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
    Title
    Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term
    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 that experienced an SAE that assessed as possibly, probably, or definitely related to the study drug by the investigator was summarized.
    Time Frame
    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
    Title
    Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term
    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 discontinued during the 44 week extension due to an AE regardless of completion status were summarized.
    Time Frame
    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 Measure Information:
    Title
    Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period
    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.
    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 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
    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
    https://www.merck.com/clinical-trials/pdf/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

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs