Trial Outcomes & Findings for Efficacy of Losartan + Amlodipine Compared to Amlodipine Alone in the Treatment of Uncontrolled High Blood Pressure (MK-0954F-399) (NCT NCT01277822)
NCT ID: NCT01277822
Last Updated: 2024-06-20
Results Overview
Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
COMPLETED
PHASE4
334 participants
Baseline and Week 8
2024-06-20
Participant Flow
Participant milestones
| Measure |
Losartan/Amlodipine
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
168
|
166
|
|
Overall Study
COMPLETED
|
153
|
155
|
|
Overall Study
NOT COMPLETED
|
15
|
11
|
Reasons for withdrawal
| Measure |
Losartan/Amlodipine
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
7
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Contraindicated medication used
|
2
|
1
|
|
Overall Study
Participant moved
|
1
|
0
|
Baseline Characteristics
Efficacy of Losartan + Amlodipine Compared to Amlodipine Alone in the Treatment of Uncontrolled High Blood Pressure (MK-0954F-399)
Baseline characteristics by cohort
| Measure |
Losartan/Amlodipine
n=168 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=166 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
Total
n=334 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
51.8 years
STANDARD_DEVIATION 10.6 • n=7 Participants
|
52.9 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
126 Participants
n=5 Participants
|
130 Participants
n=7 Participants
|
256 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 8Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Outcome measures
| Measure |
Losartan/Amlodipine
n=162 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=160 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
|
-10.1 mmHg
Standard Deviation 7.6
|
-8.8 mmHg
Standard Deviation 7.8
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Diastolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Outcome measures
| Measure |
Losartan/Amlodipine
n=156 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=156 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4
|
-9.3 mmHg
Standard Deviation 7.8
|
-10.0 mmHg
Standard Deviation 7.9
|
SECONDARY outcome
Timeframe: Baseline and Week 8Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Systolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Outcome measures
| Measure |
Losartan/Amlodipine
n=162 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=160 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
|
-15.0 mmHg
Standard Deviation 12.1
|
-12.7 mmHg
Standard Deviation 10.7
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Systolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.
Outcome measures
| Measure |
Losartan/Amlodipine
n=156 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=156 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4
|
-12.5 mmHg
Standard Deviation 13.2
|
-12.3 mmHg
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: Week 8Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Participants were evaluated at Week 8 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.
Outcome measures
| Measure |
Losartan/Amlodipine
n=162 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=160 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieve Target Blood Pressure at Week 8
|
63.0 Percentage of Participants
|
58.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 4Population: Full Analysis Set defined as all participants who were randomized, took at least 1 dose of study drug, and had blood pressure measurements at baseline and at least 1 post-randomization blood pressure measurement.
Participants were evaluated at Week 4 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) \<90mmHg or sitting systolic BP (sitSBP) \<140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.
Outcome measures
| Measure |
Losartan/Amlodipine
n=156 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=156 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieve Target Blood Pressure at Week 4
|
55.1 Percentage of Participants
|
61.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: up to 8 weeksPopulation: Safety Set defined as all participants who received at least 1 dose of study drug.
A pitting assessment of edema on both legs was performed at baseline and throughout the study. Participants were assessed in a seated position with both feet extended and the right ankle in a neutral dorsiflexion position. The index finger was pressed firmly over the bony prominence approximately 3cm proximal to the midpoint of the medial malleolus of the right ankle and will be held for three seconds. Presence of a residual indentation in the area after releasing pressure on the index finger was considered positive for pitting edema.
Outcome measures
| Measure |
Losartan/Amlodipine
n=168 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=166 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Had Peripheral Edema During the Study
|
6.5 Percentage of Participants
|
5.4 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 8Population: All participants who received at least 1 dose of study drug and had available data for ankle circumference.
Each ankle was marked with a semi-permanent marker at approximately 3 cm proximal to the midpoint of the medial malleolus to aid consistency in the performance of the measurements. Ankle circumference was measured in both ankles at baseline and Week 8 using a tension controlled tape to minimize error.
Outcome measures
| Measure |
Losartan/Amlodipine
n=163 Participants
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
|
Amlodipine
n=161 Participants
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Change From Baseline in Ankle Circumference at Week 8
Right Ankle
|
-0.5 mm
Standard Deviation 4.0
|
-0.2 mm
Standard Deviation 4.2
|
|
Change From Baseline in Ankle Circumference at Week 8
Left Ankle
|
-0.6 mm
Standard Deviation 4.7
|
-0.7 mm
Standard Deviation 4.4
|
Adverse Events
Losartan 100mg/Amlodipine 5mg
Amlodipine 10mg
Serious adverse events
| Measure |
Losartan 100mg/Amlodipine 5mg
n=168 participants at risk
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks
|
Amlodipine 10mg
n=166 participants at risk
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.60%
1/168 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.00%
0/166 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
General disorders
ASTHENIA
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE
|
1.8%
3/168 • Number of events 3 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
1.2%
2/166 • Number of events 2 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
EXCORIATION
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
FACIAL BONES FRACTURE
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
FRACTURE
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
THORACIC VERTEBRAL FRACTURE
|
0.60%
1/168 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.00%
0/166 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 2 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 2 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Renal and urinary disorders
HAEMATURIA
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Renal and urinary disorders
PROTEINURIA
|
0.00%
0/168 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.60%
1/166 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
0.60%
1/168 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.00%
0/166 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
|
0.60%
1/168 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.00%
0/166 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.60%
1/168 • Number of events 1 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
0.00%
0/166 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Losartan 100mg/Amlodipine 5mg
n=168 participants at risk
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks
|
Amlodipine 10mg
n=166 participants at risk
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
|
|---|---|---|
|
Nervous system disorders
HEADACHE
|
3.6%
6/168 • Number of events 6 • 10 weeks
Safety Set defined as all participants who received at least 1 dose of study drug.
|
6.6%
11/166 • Number of events 11 • 10 weeks
Safety Set defined as all participants who 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
- Publication restrictions are in place