Trial Outcomes & Findings for MK-0954E Study in Participants With Hypertension (MK-0954E-357) (NCT NCT01302691)
NCT ID: NCT01302691
Last Updated: 2019-03-15
Results Overview
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.
COMPLETED
PHASE3
327 participants
Baseline and Week 8
2019-03-15
Participant Flow
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.
Participant milestones
| Measure |
L50/H12.5/A5
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.
|
L50 + A5
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
164
|
163
|
|
Overall Study
COMPLETED
|
154
|
157
|
|
Overall Study
NOT COMPLETED
|
10
|
6
|
Reasons for withdrawal
| Measure |
L50/H12.5/A5
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.
|
L50 + A5
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Blood Pressure/Potassium Criteria Met
|
6
|
4
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
MK-0954E Study in Participants With Hypertension (MK-0954E-357)
Baseline characteristics by cohort
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
Total
n=327 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.9 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
55.4 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
55.2 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
131 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
253 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 8Population: 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
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.
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)
|
-9.1 mmHg
Interval -10.2 to -7.9
|
-8.0 mmHg
Interval -9.1 to -6.8
|
PRIMARY outcome
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Experience ≥1 Adverse Event (AE)
|
30.5 Percentage of Participants
|
28.8 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Experience ≥1 Drug-related AE
|
11.6 Percentage of Participants
|
3.7 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)
|
0.6 Percentage of Participants
|
0.6 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)Population: All randomized participants who received at least 1 dose of study drug.
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
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Experience ≥1 Drug-related SAE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 8 weeksPopulation: All randomized participants who received at least 1 dose of study drug.
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
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Had Study Drug Stopped Due to an AE
|
1.2 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 8Population: 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
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.
Outcome measures
| Measure |
L50/H12.5/A5
n=164 Participants
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.
|
L50 + A5
n=163 Participants
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)
|
-13.4 mmHg
Interval -15.2 to -11.6
|
-10.2 mmHg
Interval -12.0 to -8.4
|
Adverse Events
L50/H12.5/A5
L50 + A5
Serious adverse events
| Measure |
L50/H12.5/A5
n=164 participants at risk
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.
|
L50 + A5
n=163 participants at risk
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
General disorders
Sudden cardiac death
|
0.00%
0/164 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
0.61%
1/163 • Number of events 1 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.61%
1/164 • Number of events 1 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
0.00%
0/163 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.61%
1/164 • Number of events 1 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
0.00%
0/163 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.61%
1/164 • Number of events 1 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
0.00%
0/163 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
Other adverse events
| Measure |
L50/H12.5/A5
n=164 participants at risk
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.
|
L50 + A5
n=163 participants at risk
Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
6.7%
11/164 • Number of events 11 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
9.2%
15/163 • Number of events 15 • up to 2 weeks after last dose of study drug (up to 10 weeks)
All participants that received at least 1 dose of study drug.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck, Sharp & Dohme Corp.
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