Clinical trial NCT01299376: MK-0954E Phase III Long-Term Study in Participants With Hypertension (MK-0954E-356)
Official title: 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 MK-954H (L50/H12.5 mg) [PREMINENT®] and an Open-label, Long-term Clinical Trial to Study the Safety of MK-0954E
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Essential hypertension
Antihypertensive agents
Blood pressure
Uncontrolled hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-02-18
Enrollment: 286
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study has two parts. In the first part, the efficacy and safety MK-0954E (losartan potassium 50 mg \[L50\] (+) hydrochlorothiazide 12.5 mg \[H12.5\] (+) amlodipine besylate 5mg \[A5\]) will be evaluated and compared to the efficacy and safety of MK-0954H (L50/H12.5) in Japanese participants. In the second part, the safety and tolerability of long-term use of open-label MK-0954E in participants with hypertension will be evaluated. The primary hypothesis is that MK-0954E is more effective in lowering mean trough sitting diastolic blood pressure (SiDBP) after 8 weeks of treatment compared to MK-954H (L50/H12.5 mg) in Japanese participants with essential hypertension who are not adequately controlled following a 8-week treatment with filter period study drug of MK-954H.


Eligibility criteria: Inclusion criteria:

* Participant has a diagnosis of essential hypertension
* Participant is being treated with a single, or dual combination 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

Primary outcomes:
measure: Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period
timeFrame: Baseline and Week 8
measure: Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period
timeFrame: up to Week 8
measure: Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period
timeFrame: up to Week 8
measure: Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period
timeFrame: up to Week 8
measure: Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period
timeFrame: up to Week 8
measure: Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period
timeFrame: up to Week 8
measure: Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term
timeFrame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
measure: Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term
timeFrame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
measure: Percentage of Participants Who Experience 1 or More SAEs- Long Term
timeFrame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
measure: Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term
timeFrame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
measure: Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term
timeFrame: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5
Secondary outcomes:
measure: Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.