A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009 AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01370655
First received: June 8, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This study is being done to evaluate the antihypertensive efficacy and tolerability of MK-7145 in participants with mild-to-moderate hypertension.


Condition Intervention Phase
Hypertension
Drug: MK-7145
Drug: Hydrochlorothiazide (HCTZ)
Drug: Placebo to MK-7145
Drug: Placebo to HCTZ
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase Ib, Randomized, Double-Blind, 4-Treatment, 2-Period Incomplete Block Study to Evaluate the Multiple Dose Effects of MK-7145 and Hydrochlorothiazide Compared to Placebo on Blood Pressure in Male Patients With Hypertension

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Time-weighted average over 24 hours post dose (TWA [0-24]) in systolic blood pressure (SBP) with MK-7145 6 mg versus placebo [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • TWA[0-24] in systolic blood pressure (SBP) with MK-7145 6 mg versus hydrochlorothiazide (HCTZ) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Urinary sodium excretion (UNaV) for MK-7145 6 mg versus placebo [ Time Frame: 24 hours post dose on Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • TWA[0-24] in diastolic blood pressure (DBP) with MK-7145 6 mg versus HCTZ [ Time Frame: From baseline up to Day 28 ] [ Designated as safety issue: No ]
  • TWA[0-24] in SBP with MK-7145 6 mg versus MK-7145 3 mg [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • TWA [0-24] in DBP with MK-7145 6 mg versus MK-7145 3 mg [ Time Frame: From baseline up to Day 28 ] [ Designated as safety issue: No ]
  • Difference in urinary sodium excretion for MK-7145 6 mg versus placebo [ Time Frame: 24 hours post dose on Day 1 ] [ Designated as safety issue: No ]
  • Difference in urinary potassium excretion for MK-7145 versus placebo [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: June 2011
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-7145 6 mg Drug: MK-7145
MK-7145, capsules, orally, 6 mg in 2 divided doses (3 mg and 3 mg, given 4 hours apart) per day
Drug: Placebo to HCTZ
placebo capsules, orally, two capsules, once daily
Experimental: MK-7145 3 mg Drug: MK-7145
MK-7145, capsules, orally, 3 mg in 2 divided doses (2 mg and 1 mg, given 4 hours apart) per day
Drug: Placebo to MK-7145
placebo capsules, orally, twice per day (given 4 hours apart)
Drug: Placebo to HCTZ
placebo capsules, orally, two capsules, once daily
Active Comparator: Hydrochlorothiazide Drug: Hydrochlorothiazide (HCTZ)
HCTZ, capsules, orally, two 12.5 mg capsules, once daily
Drug: Placebo to MK-7145
placebo capsules, orally, twice per day (given 4 hours apart)
Placebo Comparator: Placebo Drug: Placebo to MK-7145
placebo capsules, orally, twice per day (given 4 hours apart)
Drug: Placebo to HCTZ
placebo capsules, orally, two capsules, once daily

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Diagnosis of essential hypertension
  • Body mass index (BMI) ≤35 kg/m^2
  • Participant in general good health
  • No history of clinically significant arrhythmias or clinically significant abnormality on electrocardiogram (ECG)
  • No history of clinically significant cardiac disease
  • Treatment-naïve or taking up to 2 antihypertensive therapeutic agents
  • Non-smoker and/or has not used nicotine or nicotine-containing products for at least 6 months

Exclusion criteria:

  • Participant has low plasma potassium
  • History of stroke, chronic seizures, or major neurological disorder
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • History of osteoporosis
  • Active or history of nephrocalcinosis, nephrolithiasis or hypercalciuria
  • Orthostatic change in vital sign measurements while going from a semi-recumbent to standing position accompanied by symptoms
  • Functional disability that can interfere with rising from a semi-recumbent position to the standing position
  • History of malignant neoplastic disease. Exceptions: (1) adequately treated non-melanomatous skin carcinoma; (2) other malignancies which have been successfully treated >10 years prior to the prestudy (screening) visit, (3) unlikely to sustain a recurrence
  • Participant is unable to refrain from the use of prescription and non-prescription drugs such as high-dose aspirin (≥325 mg/day), strong/moderate Cytochrome P450 3A4 (CYP3A4) inhibitors (such as ritonavir, indinavir, nelfinavir, erythromycin, telithromycin, clarithromycin, chloramphenicol, fluconazole, ketoconazole, itraconazole, nefazodone, aprepitant, verapamil, or diltiazem) as well as strong/moderate CYP3A4 inducers (such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, efavirenz, nevirapine, etravirine, rifampicin, modafinil, St Johns Wort, cyproterone, or progestin) beginning approximately 2 weeks (or 5 half-lives), prior to administration of the initial dose of study drug until the post study visit
  • Current use of non-steroidal anti-inflammatory drugs (NSAIDs) other than low dose aspirin, aluminum- or magnesium-containing antacids, sucralfate, metal cations such as iron, multivitamins containing iron or zinc that cannot be discontinued at least 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug until the post study visit
  • Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
  • Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
  • Major surgery, donation or lost 1 unit of blood (approximately 500 mL), or participation in another investigational study within 4 weeks prior to the prestudy (screening)
  • History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Regular use of any illicit drugs or history of drug abuse within approximately 6 months
  • Dehydration or volume-depletion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01370655     History of Changes
Other Study ID Numbers: 7145-009
Study First Received: June 8, 2011
Last Updated: May 7, 2014
Health Authority: South Africa: Medicines Control Council

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014