Trial Outcomes & Findings for A Long-term Study of the Safety of MK-0954A in Patients With Essential Hypertension (MK-0954A-351) (NCT NCT01307033)
NCT ID: NCT01307033
Last Updated: 2024-05-17
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
278 participants
Primary outcome timeframe
Up to 52 weeks
Results posted on
2024-05-17
Participant Flow
Participant milestones
| Measure |
MK-0954H (L50/H12.5) Double Blind Period (Period 1)
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5)
|
MK-0954A (L100/H12.5) Double Blind Period (Period 1)
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5)
|
L50/H12.5→L100/H12.5 Open Label (Period 2)
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)
|
L100/H12.5→L100/H12.5 Open Label (Period 2)
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
|
|---|---|---|---|---|
|
8-week Double-blind Period
STARTED
|
144
|
134
|
0
|
0
|
|
8-week Double-blind Period
COMPLETED
|
131
|
127
|
0
|
0
|
|
8-week Double-blind Period
NOT COMPLETED
|
13
|
7
|
0
|
0
|
|
44-week Open-label Extension
STARTED
|
0
|
0
|
131
|
127
|
|
44-week Open-label Extension
COMPLETED
|
0
|
0
|
120
|
115
|
|
44-week Open-label Extension
NOT COMPLETED
|
0
|
0
|
11
|
12
|
Reasons for withdrawal
| Measure |
MK-0954H (L50/H12.5) Double Blind Period (Period 1)
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5)
|
MK-0954A (L100/H12.5) Double Blind Period (Period 1)
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5)
|
L50/H12.5→L100/H12.5 Open Label (Period 2)
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)
|
L100/H12.5→L100/H12.5 Open Label (Period 2)
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
|
|---|---|---|---|---|
|
8-week Double-blind Period
Adverse Event
|
2
|
0
|
0
|
0
|
|
8-week Double-blind Period
Withdrawal by Subject
|
4
|
1
|
0
|
0
|
|
8-week Double-blind Period
Lack of Efficacy
|
1
|
0
|
0
|
0
|
|
8-week Double-blind Period
Blood Pressure Withdrawal Criteria Met
|
0
|
3
|
0
|
0
|
|
8-week Double-blind Period
Potassium Withdrawal Criteria Met
|
6
|
3
|
0
|
0
|
|
44-week Open-label Extension
Adverse Event
|
0
|
0
|
2
|
1
|
|
44-week Open-label Extension
Withdrawal by Subject
|
0
|
0
|
2
|
1
|
|
44-week Open-label Extension
Physician Decision
|
0
|
0
|
1
|
0
|
|
44-week Open-label Extension
Blood Pressure Withdrawal Criteria Met
|
0
|
0
|
0
|
2
|
|
44-week Open-label Extension
Potassium Withdrawal Criteria Met
|
0
|
0
|
6
|
7
|
|
44-week Open-label Extension
Death
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Long-term Study of the Safety of MK-0954A in Patients With Essential Hypertension (MK-0954A-351)
Baseline characteristics by cohort
| Measure |
MK-0954H (L50/H12.5)
n=144 Participants
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)
|
MK-0954A (L100/H12.5)
n=134 Participants
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
n=278 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.9 Years
STANDARD_DEVIATION 10.7 • n=93 Participants
|
57.8 Years
STANDARD_DEVIATION 10.8 • n=4 Participants
|
57.3 Years
STANDARD_DEVIATION 10.7 • n=27 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
73 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
103 Participants
n=93 Participants
|
102 Participants
n=4 Participants
|
205 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Up to 52 weeksPopulation: 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).
Outcome measures
| Measure |
MK-0954H (L50/H12.5)
n=131 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5).
|
MK-0954A (L100/H12.5)
n=134 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5).
|
|---|---|---|
|
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)
|
71.0 Percentage of Participants
|
72.4 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 8 (End of Double-blind Period)Population: 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
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.
Outcome measures
| Measure |
MK-0954H (L50/H12.5)
n=144 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5).
|
MK-0954A (L100/H12.5)
n=134 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5).
|
|---|---|---|
|
Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8
|
-5.3 mmHg
95% Confidence Interval 0.7 • Interval -6.6 to -3.9
|
-5.0 mmHg
95% Confidence Interval 0.7 • Interval -6.4 to -3.6
|
SECONDARY outcome
Timeframe: Baseline and Week 8 (End of Double-blind Period)Population: 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
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.
Outcome measures
| Measure |
MK-0954H (L50/H12.5)
n=144 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5).
|
MK-0954A (L100/H12.5)
n=134 Participants
One combination tablet daily for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5).
|
|---|---|---|
|
Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8
|
-6.2 mmHg
Interval -8.2 to -4.3
|
-8.5 mmHg
Interval -10.5 to -6.5
|
Adverse Events
MK-0954H (L50/H12.5) Double Blind Period (Period 1)
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
MK-0954A (L100/H12.5) Double Blind Period (Period 1)
Serious events: 2 serious events
Other events: 20 other events
Deaths: 0 deaths
L50/H12.5→L100/H12.5 Open Label (Period 2)
Serious events: 6 serious events
Other events: 47 other events
Deaths: 0 deaths
L100/H12.5→L100/H12.5 Open Label (Period 2)
Serious events: 1 serious events
Other events: 43 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MK-0954H (L50/H12.5) Double Blind Period (Period 1)
n=144 participants at risk
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5)
|
MK-0954A (L100/H12.5) Double Blind Period (Period 1)
n=134 participants at risk
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5)
|
L50/H12.5→L100/H12.5 Open Label (Period 2)
n=131 participants at risk
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)
|
L100/H12.5→L100/H12.5 Open Label (Period 2)
n=127 participants at risk
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
|
|---|---|---|---|---|
|
Infections and infestations
Abscess neck
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.75%
1/134 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/131 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Limb crushing injury
|
0.69%
1/144 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/131 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.75%
1/134 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/131 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/131 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.79%
1/127 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.76%
1/131 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/127 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
Other adverse events
| Measure |
MK-0954H (L50/H12.5) Double Blind Period (Period 1)
n=144 participants at risk
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 50 mg (L50) and 12.5 mg of hydrochlorothiazide (H12.5)
|
MK-0954A (L100/H12.5) Double Blind Period (Period 1)
n=134 participants at risk
One combination tablet daily, orally, for 8 weeks. Each tablet contains Losartan 100 mg (L100) and 12.5 mg of hydrochlorothiazide (H12.5)
|
L50/H12.5→L100/H12.5 Open Label (Period 2)
n=131 participants at risk
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)
|
L100/H12.5→L100/H12.5 Open Label (Period 2)
n=127 participants at risk
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
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.6%
11/144 • Number of events 13 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
7.5%
10/134 • Number of events 11 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
16.8%
22/131 • Number of events 36 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
21.3%
27/127 • Number of events 34 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.69%
1/144 • Number of events 1 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
7.6%
10/131 • Number of events 10 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
5.5%
7/127 • Number of events 7 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Investigations
Blood uric acid increased
|
4.9%
7/144 • Number of events 7 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
6.0%
8/134 • Number of events 8 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
4.6%
6/131 • Number of events 6 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
2.4%
3/127 • Number of events 3 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/134 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
5.3%
7/131 • Number of events 7 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
3.9%
5/127 • Number of events 5 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/144 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
1.5%
2/134 • Number of events 3 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
5.3%
7/131 • Number of events 8 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
3.1%
4/127 • Number of events 9 • 52 weeks
All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of study treatment.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER