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

A Phase III, Randomized, Active-Comparator Controlled Clinical Trial to Study the Efficacy and Safety of MK-0954E in Japanese Patients With Essential Hypertension Uncontrolled With Losartan and Amlodipine Co-administration

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01302691

Enrollment

327

Registered

2011-02-24

Start date

2011-01-01

Completion date

2012-04-01

Last updated

2019-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension

Keywords

Essential hypertension, Uncontrolled hypertension, Antihypertensive agents, Blood pressure

Brief summary

This study is being done to evaluate the efficacy, safety, and tolerability of losartan potassium 50 mg (L50) + hydrochlorothiazide 12.5 mg (H12.5) + amlodipine besylate 5 mg (A5) (MK-0954E). The primary hypothesis is that L50/H12.5/A5 is more effective in lowering mean trough sitting diastolic blood pressure (SiDBP) after 8 weeks of treatment compared to L50+A5 in Japanese participants with essential hypertension who are not adequately controlled following an 8-week treatment with filter period study drug (L50+A5).

Interventions

DRUGlosartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E)

One tablet, containing 50 mg losartan potassium, 12.5 mg hydrochlorothiazide, and 5 mg amlodipine besylate, orally, once daily, for 8 weeks.

DRUGLosartan potassium

One tablet, containing 50 mg losartan potassium, orally, once daily, for 8 weeks.

DRUGAmlodipine besylate

One capsule, containing 5 mg amlodipine besylate, orally, once daily, for 8 weeks.

DRUGPlacebo to MK-0954E

One tablet, containing placebo, orally, once daily, for 8 weeks.

DRUGPlacebo to losartan potassium

One tablet, containing placebo, orally, once daily, for 8 weeks.

DRUGPlacebo to amlodipine besylate

One capsule, containing placebo, orally, once daily, for 8 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

20 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Participant has a diagnosis of essential hypertension. * Participant is being treated with single or dual treatment for hypertension and will be able to discontinue the prior antihypertensive medication. * Participant has a mean trough SiDBP of ≥ 90 mmHg and \< 110 mmHg. * Participant has a mean trough SiSBP of ≥ 140 mmHg and \< 200 mmHg. * Participant has no clinically significant abnormality at screening visit.

Exclusion criteria

* Participant is currently taking \> 2 antihypertensive medications. * Participant has a history of significant multiple and/or severe allergies to ingredients of Nu-Lotan or Preminent, amlodipine or dihydropyridine drug, and thiazide drug or related drug (i.e., sulfonamide-containing chlortalidone medicines). * Participant is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history within the last year of drug or alcohol abuse or dependence. * Participant is pregnant or breastfeeding, or expecting to conceive OR the pregnancy test is positive at screening visit (Visit 1). * Participant is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Experience ≥1 Drug-related AE	up to 14 days after last dose of study drug (up to 10 weeks)	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.
Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)	Baseline and Week 8	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.
Percentage of Participants Who Experience ≥1 Adverse Event (AE)	up to 14 days after last dose of study drug (up to 10 weeks)	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.
Percentage of Participants Who Had Study Drug Stopped Due to an AE	up to 8 weeks	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
Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)	up to 14 days after last dose of study drug (up to 10 weeks)	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.
Percentage of Participants Who Experience ≥1 Drug-related SAE	up to 14 days after last dose of study drug (up to 10 weeks)	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

Secondary

Measure	Time frame	Description
Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)	Baseline and Week 8	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.

Participant flow

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.

Participants by arm

Arm	Count
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.	164
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.	163
Total	327

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Blood Pressure/Potassium Criteria Met	6	4
Overall Study	Death	0	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	0	1
Overall Study	Protocol Violation	1	0

Baseline characteristics

Characteristic	Total	L50/H12.5/A5	L50 + A5
Age, Continuous	55.2 years STANDARD_DEVIATION 9.7	54.9 years STANDARD_DEVIATION 9.4	55.4 years STANDARD_DEVIATION 10.1
Sex: Female, Male Female	74 Participants	33 Participants	41 Participants
Sex: Female, Male Male	253 Participants	131 Participants	122 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	11 / 164	15 / 163
serious Total, serious adverse events	1 / 164	1 / 163

Outcome results

Primary

Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)

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

Population: 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	Measure	Value (LEAST_SQUARES_MEAN)
L50/H12.5/A5	Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)	-9.1 mmHg
L50 + A5	Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)	-8.0 mmHg

p-value: 0.20595% CI: [-2.7, 0.6]Constrained Longitudinal Data Analysis

Primary

Percentage of Participants Who Experience ≥1 Adverse Event (AE)

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)