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Trial record 50 of 73 for:    HYDROCHLOROTHIAZIDE AND LOSARTAN

A Long-term Study of the Safety of MK-0954A in Patients With Essential Hypertension (MK-0954A-351)

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ClinicalTrials.gov Identifier: NCT01307033
Recruitment Status : Completed
First Posted : March 2, 2011
Results First Posted : January 6, 2014
Last Update Posted : May 5, 2017
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: MK-0954A
Drug: MK-954H
Drug: Placebo to MK-0954A
Drug: Placebo to MK-954H
Enrollment 278
Recruitment Details  
Pre-assignment Details  
Arm/Group Title MK-0954H (L50/H12.5) Double Blind Period (Period 1) MK-0954A (L100/H12.5) Double Blind Period (Period 1) L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Hide Arm/Group Description One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will then receive open label MK-0954A (L100/H12.5) orally, once daily for 44 weeks (extension) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will continue to receive MK-0954A orally, once daily for 44 week extension
Period Title: 8-week Double-blind Period
Started 144 134 0 0
Completed 131 127 0 0
Not Completed 13 7 0 0
Reason Not Completed
Adverse Event             2             0             0             0
Withdrawal by Subject             4             1             0             0
Lack of Efficacy             1             0             0             0
Blood Pressure Withdrawal Criteria Met             0             3             0             0
Potassium Withdrawal Criteria Met             6             3             0             0
Period Title: 44-week Open-label Extension
Started 0 0 131 127
Completed 0 0 120 115
Not Completed 0 0 11 12
Reason Not Completed
Adverse Event             0             0             2             1
Withdrawal by Subject             0             0             2             1
Physician Decision             0             0             1             0
Blood Pressure Withdrawal Criteria Met             0             0             0             2
Potassium Withdrawal Criteria Met             0             0             6             7
Death             0             0             0             1
Arm/Group Title MK-0954H (L50/H12.5) MK-0954A (L100/H12.5) Total
Hide Arm/Group Description One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will then receive open label MK-0954A (L100/H12.5) orally, once daily for 44 weeks (extension) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will continue to receive MK-0954A orally, once daily for 44 week extension. Total of all reporting groups
Overall Number of Baseline Participants 144 134 278
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 144 participants 134 participants 278 participants
56.9  (10.7) 57.8  (10.8) 57.3  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 134 participants 278 participants
Female
41
  28.5%
32
  23.9%
73
  26.3%
Male
103
  71.5%
102
  76.1%
205
  73.7%
1.Primary Outcome
Title Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension)
Hide Description [Not Specified]
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All-Patients-as-Treated (APaT) Population, which consists of all randomized patients who received at least one dose of MK-0954A. The L100/H12.5 (L50/H12.5) arm only includes data from extension period (44 weeks); L100/H12.5→L100/H12.5 Open Label arm includes data from entire study period (52 weeks).
Arm/Group Title L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Hide Arm/Group Description:
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will then receive open label MK-0954A (L100/H12.5) orally, once daily for 44 weeks (extension)
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will continue to receive MK-0954A orally, once daily for 44 week extension
Overall Number of Participants Analyzed 131 134
Measure Type: Number
Unit of Measure: Percentage of Participants
71.0 72.4
2.Secondary Outcome
Title Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8
Hide Description Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings.
Time Frame Baseline and Week 8 (End of Double-blind Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population: defined as all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that required baseline data
Arm/Group Title MK-0954H (L50/H12.5) MK-0954A (L100/H12.5)
Hide Arm/Group Description:
One combination tablet daily for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5).
One combination tablet daily for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5).
Overall Number of Participants Analyzed 144 134
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-5.3
(-6.6 to -3.9)
-5.0
(-6.4 to -3.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK-0954H (L50/H12.5), MK-0954A (L100/H12.5)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Constained logitudinal data analysis
Comments Model included treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.7 to 2.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8
Hide Description Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings.
Time Frame Baseline and Week 8 (End of Double-blind Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population: defined as all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that required baseline data
Arm/Group Title MK-0954H (L50/H12.5) MK-0954A (L100/H12.5)
Hide Arm/Group Description:
One combination tablet daily for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5)
One combination tablet daily for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5)
Overall Number of Participants Analyzed 144 134
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-6.2
(-8.2 to -4.3)
-8.5
(-10.5 to -6.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK-0954H (L50/H12.5), MK-0954A (L100/H12.5)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Constained longitudinal data analysis
Comments Model included treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-5.0 to 0.5
Estimation Comments [Not Specified]
Time Frame 52 weeks
Adverse Event Reporting Description All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title MK-0954H (L50/H12.5) Double Blind Period (Period 1) MK-0954A (L100/H12.5) Double Blind Period (Period 1) L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Hide Arm/Group Description One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will then receive open label MK-0954A (L100/H12.5) orally, once daily for 44 weeks (extension) One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5). Participants will continue to receive MK-0954A orally, once daily for 44 week extension
All-Cause Mortality
MK-0954H (L50/H12.5) Double Blind Period (Period 1) MK-0954A (L100/H12.5) Double Blind Period (Period 1) L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
MK-0954H (L50/H12.5) Double Blind Period (Period 1) MK-0954A (L100/H12.5) Double Blind Period (Period 1) L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/144 (0.69%)      2/134 (1.49%)      6/131 (4.58%)      1/127 (0.79%)    
Cardiac disorders         
Atrial fibrillation   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Ear and labyrinth disorders         
Vertigo   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Gastrointestinal disorders         
Ileus   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Vomiting   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Infections and infestations         
Abscess neck   0/144 (0.00%)  0 1/134 (0.75%)  1 0/131 (0.00%)  0 0/127 (0.00%)  0
Injury, poisoning and procedural complications         
Limb crushing injury   1/144 (0.69%)  1 0/134 (0.00%)  0 0/131 (0.00%)  0 0/127 (0.00%)  0
Lower limb fracture   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Spinal column stenosis   0/144 (0.00%)  0 1/134 (0.75%)  1 0/131 (0.00%)  0 0/127 (0.00%)  0
Nervous system disorders         
Carotid artery stenosis   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Cerebral infarction   0/144 (0.00%)  0 0/134 (0.00%)  0 1/131 (0.76%)  1 0/127 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism   0/144 (0.00%)  0 0/134 (0.00%)  0 0/131 (0.00%)  0 1/127 (0.79%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MK-0954H (L50/H12.5) Double Blind Period (Period 1) MK-0954A (L100/H12.5) Double Blind Period (Period 1) L50/H12.5→L100/H12.5 Open Label (Period 2) L100/H12.5→L100/H12.5 Open Label (Period 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/144 (12.50%)      20/134 (14.93%)      47/131 (35.88%)      43/127 (33.86%)    
Infections and infestations         
Nasopharyngitis   11/144 (7.64%)  13 10/134 (7.46%)  11 22/131 (16.79%)  36 27/127 (21.26%)  34
Upper respiratory tract infection   1/144 (0.69%)  1 0/134 (0.00%)  0 10/131 (7.63%)  10 7/127 (5.51%)  7
Investigations         
Blood uric acid increased   7/144 (4.86%)  7 8/134 (5.97%)  8 6/131 (4.58%)  6 3/127 (2.36%)  3
Metabolism and nutrition disorders         
Diabetes mellitus   0/144 (0.00%)  0 0/134 (0.00%)  0 7/131 (5.34%)  7 5/127 (3.94%)  5
Respiratory, thoracic and mediastinal disorders         
Upper respiratory tract inflammation   0/144 (0.00%)  0 2/134 (1.49%)  3 7/131 (5.34%)  8 4/127 (3.15%)  9
Indicates events were collected by systematic assessment
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: NCT01307033     History of Changes
Other Study ID Numbers: 0954A-351
First Submitted: March 1, 2011
First Posted: March 2, 2011
Results First Submitted: November 14, 2013
Results First Posted: January 6, 2014
Last Update Posted: May 5, 2017