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

NCT01302691 | Completed Phase 3 Results

• 1 other identifier: 0954E-357
• Study Type: interventional
• Target: 327
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hypertension

Keywords

Essential hypertension; Uncontrolled hypertension; Antihypertensive agents; Blood pressure

Outcome Measures

Primary Outcomes (6)

• 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.

  Baseline and Week 8

• 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.

  up to 14 days after last dose of study drug (up to 10 weeks)

• Percentage of Participants Who Experience ≥1 Drug-related 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. 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.

  up to 14 days after last dose of study drug (up to 10 weeks)

• Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)

  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.

  up to 14 days after last dose of study drug (up to 10 weeks)

• Percentage of Participants Who Experience ≥1 Drug-related SAE

  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

  up to 14 days after last dose of study drug (up to 10 weeks)

• Percentage of Participants Who Had Study Drug Stopped Due to an 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 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

  up to 8 weeks

Secondary Outcomes (1)

• Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)

  Baseline and Week 8

Study Arms (2)

L50/H12.5/A5

EXPERIMENTAL

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.

Drug: losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E); Drug: Placebo to losartan potassium; Drug: Placebo to amlodipine besylate

L50 + A5

ACTIVE COMPARATOR

Participants receive tablet, containing 50 mg losartan potassium (L50), and tablet containing 5 mg amlodipine besylate (A5), orally, once daily, for 8 weeks.

Drug: Losartan potassium; Drug: Amlodipine besylate; Drug: Placebo to MK-0954E

Interventions

losartan potassium + hydrochlorothiazide + amlodipine besylate (MK-0954E) DRUG

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

L50/H12.5/A5

Losartan potassium DRUG

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

L50 + A5

Amlodipine besylate DRUG

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

L50 + A5

Placebo to MK-0954E DRUG

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

L50 + A5

Placebo to losartan potassium DRUG

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

L50/H12.5/A5

Placebo to amlodipine besylate DRUG

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

L50/H12.5/A5

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Rakugi H, Tsuchihashi T, Shimada K, Numaguchi H, Nishida C, Yamaguchi H, Shirakawa M, Azuma K, Fujita KP. Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clin Exp Hypertens. 2015;37(3):260-6. doi: 10.3109/10641963.2014.954712. Epub 2014 Oct 1.

  PMID: 25271811 RESULT

• Rakugi H, Tsuchihashi T, Shimada K, Numaguchi H, Nishida C, Yamaguchi H, Shirakawa M, Azuma K, Fujita KP. Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg. Hypertens Res. 2015 May;38(5):329-35. doi: 10.1038/hr.2015.3. Epub 2015 Feb 26.

  PMID: 25716649 RESULT

MeSH Terms

Conditions

Hypertension; Essential Hypertension

Interventions

Losartan; Hydrochlorothiazide; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck, Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2011
• First Posted: February 24, 2011
• Study Start: January 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: March 15, 2019
• Results First Posted: January 27, 2017

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share