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Trial record 40 of 73 for:    HYDROCHLOROTHIAZIDE AND LOSARTAN

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

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ClinicalTrials.gov Identifier: NCT01302691
Recruitment Status : Completed
First Posted : February 24, 2011
Results First Posted : January 27, 2017
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hypertension
Interventions 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
Enrollment 327
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Period Title: Overall Study
Started 164 163
Completed 154 157
Not Completed 10 6
Reason Not Completed
Adverse Event             2             0
Death             0             1
Lost to Follow-up             1             0
Blood Pressure/Potassium Criteria Met             6             4
Physician Decision             0             1
Protocol Violation             1             0
Arm/Group Title L50/H12.5/A5 L50 + A5 Total
Hide Arm/Group 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. Total of all reporting groups
Overall Number of Baseline Participants 164 163 327
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 163 participants 327 participants
54.9  (9.4) 55.4  (10.1) 55.2  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 163 participants 327 participants
Female
33
  20.1%
41
  25.2%
74
  22.6%
Male
131
  79.9%
122
  74.8%
253
  77.4%
1.Primary Outcome
Title Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-9.1
(-10.2 to -7.9)
-8.0
(-9.1 to -6.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection L50/H12.5/A5, L50 + A5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.205
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments Model includes treatment group, time point, and the interaction of time by treatment with restriction of same baseline mean across treatment groups
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.7 to 0.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Experience ≥1 Adverse Event (AE)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: Percentage of Participants
30.5 28.8
3.Primary Outcome
Title Percentage of Participants Who Experience ≥1 Drug-related AE
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: Percentage of Participants
11.6 3.7
4.Primary Outcome
Title Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: Percentage of Participants
0.6 0.6
5.Primary Outcome
Title Percentage of Participants Who Experience ≥1 Drug-related SAE
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0
6.Primary Outcome
Title Percentage of Participants Who Had Study Drug Stopped Due to an AE
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: Percentage of Participants
1.2 0.0
7.Secondary Outcome
Title Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
Overall Number of Participants Analyzed 164 163
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-13.4
(-15.2 to -11.6)
-10.2
(-12.0 to -8.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection L50/H12.5/A5, L50 + A5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments Model includes treatment group, time point, and the interaction of time by treatment with restriction of same baseline mean across treatment groups
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-5.7 to -0.8
Estimation Comments [Not Specified]
Time Frame up to 2 weeks after last dose of study drug (up to 10 weeks)
Adverse Event Reporting Description All participants that received at least 1 dose of study drug.
 
Arm/Group Title L50/H12.5/A5 L50 + A5
Hide Arm/Group 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.
All-Cause Mortality
L50/H12.5/A5 L50 + A5
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
L50/H12.5/A5 L50 + A5
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/164 (0.61%)      1/163 (0.61%)    
General disorders     
Sudden cardiac death  1  0/164 (0.00%)  0 1/163 (0.61%)  1
Injury, poisoning and procedural complications     
Clavicle fracture  1  1/164 (0.61%)  1 0/163 (0.00%)  0
Rib fracture  1  1/164 (0.61%)  1 0/163 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pneumothorax  1  1/164 (0.61%)  1 0/163 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
L50/H12.5/A5 L50 + A5
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/164 (6.71%)      15/163 (9.20%)    
Infections and infestations     
Nasopharyngitis  1  11/164 (6.71%)  11 15/163 (9.20%)  15
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck, Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01302691     History of Changes
Other Study ID Numbers: 0954E-357
First Submitted: February 22, 2011
First Posted: February 24, 2011
Results First Submitted: December 5, 2016
Results First Posted: January 27, 2017
Last Update Posted: March 15, 2019